{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:44:20Z","timestamp":1791474260296,"version":"4.3.4"},"reference-count":103,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T00:00:00Z","timestamp":1696550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p>The modulation of inflammation is pivotal for uterine homeostasis. Here we evaluated the effect of the oestrus cycle on the expression of pro-inflammatory and anti-inflammatory markers in a cellular model of induced fibrosis. Mare endometrial stromal cells isolated from follicular or mid-luteal phase were primed with 10\u2009ng\/mL of TGF\u03b2 alone or in combination with either IL1\u03b2, IL6, or TNF\u03b1 (10\u2009ng\/mL each) or all together for 24\u2009h. Control cells were not primed. Messenger and miRNA expression were analyzed using real-time quantitative PCR (RT-qPCR). Cells in the follicular phase primed with pro-inflammatory cytokines showed higher expression of collagen-related genes (<jats:italic>CTGF, COL1A1, COL3A1<\/jats:italic>, and <jats:italic>TIMP1<\/jats:italic>) and mesenchymal marker (<jats:italic>SLUG, VIM, CDH2<\/jats:italic>, and <jats:italic>CDH11<\/jats:italic>) genes; <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.05. Cells primed during the mid-luteal overexpressed genes associated with extracellular matrix, processing, and prostaglandin E synthase (<jats:italic>MMP2, MMP9, PGR, TIMP2<\/jats:italic>, and <jats:italic>PTGES<\/jats:italic>; <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.05). There was a notable upregulation of pro-fibrotic miRNAs (miR17, miR21, and miR433) in the follicular phase when the cells were exposed to TGF\u03b2 + IL1\u03b2, TGF\u03b2 + IL6 or TGF\u03b2 + IL1\u03b2\u2009+\u2009IL6\u2009+\u2009TNF\u03b1. Conversely, in cells from the mid-luteal phase, the treatments either did not or diminished the expression of the same miRNAs. On the contrary, the anti-fibrotic miRNAs (miR26a, miR29b, miR29c, miR145, miR378, and mir488) were not upregulated with treatments in the follicular phase. Rather, they were overexpressed in cells from the mid-luteal phase, with the highest regulation observed in TGF\u03b2 + IL1\u03b2\u2009+\u2009IL6\u2009+\u2009TNF\u03b1 treatment groups. These miRNAs were also analyzed in the extracellular vesicles secreted by the cells. A similar trend as seen with cellular miRNAs was noted, where anti-fibrotic miRNAs were downregulated in the follicular phase, while notably elevated pro-fibrotic miRNAs were observed in extracellular vesicles originating from the follicular phase. Pro-inflammatory cytokines may amplify the TGF\u03b2 signal in the follicular phase resulting in significant upregulation of extracellular matrix-related genes, an imbalance in the metalloproteinases, downregulation of estrogen receptors, and upregulation of pro-fibrotic factors. Conversely, in the luteal phase, there is a protective role mediated primarily through an increase in anti-fibrotic miRNAs, a decrease in SMAD2 phosphorylation, and reduced expression of fibrosis-related genes.<\/jats:p>","DOI":"10.3389\/fvets.2023.1271240","type":"journal-article","created":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T07:11:31Z","timestamp":1696576291000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Mare stromal endometrial cells differentially modulate inflammation depending on oestrus cycle status: an in vitro study"],"prefix":"10.3389","volume":"10","author":[{"given":"Yat S.","family":"Wong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana C.","family":"Man\u00e7anares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe I.","family":"Navarrete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela M.","family":"Poblete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00eddice","family":"M\u00e9ndez-P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gra\u00e7a M. L.","family":"Ferreira-Dias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lleretny","family":"Rodriguez-Alvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fidel Ovidio","family":"Castro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1016\/j.cveq.2006.07.003","article-title":"Breeding-induced endometritis in mares","volume":"22","author":"Troedsson","year":"2006","journal-title":"Vet Clin N Am Equine Pract"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1186\/2046-0481-61-3-163","article-title":"Equine post-breeding endometritis: a review","volume":"61","author":"Maischberger","year":"2008","journal-title":"Ir Vet J"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"779","DOI":"10.3390\/ani12060779","article-title":"Evolution of the concepts of Endometrosis, post breeding endometritis, and susceptibility of mares","volume":"12","author":"Katila","year":"2022","journal-title":"Animals"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1016\/0093-691X(92)90108-4","article-title":"Relationships of age to uterine function and reproductive efficiency in mares","volume":"37","author":"Carnevale","year":"1992","journal-title":"Theriogenology"},{"key":"ref5","first-page":"64","article-title":"Postbreeding uterine fluid accumulation in a Normal population of thoroughbred mares: a field study","volume":"44","author":"Zent","year":"1998","journal-title":"Proc Am Assoc Equine Pract"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1111\/j.1439-0531.2009.01485.x","article-title":"Clinical and subclinical endometritis in the Mare: both threats to fertility","volume":"44","author":"LeBlanc","year":"2009","journal-title":"Reprod Domest Anim"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/1746-6148-8-41","article-title":"Inflammatory responses to induced infectious endometritis in mares resistant or susceptible to persistent endometritis","volume":"8","author":"Christoffersen","year":"2012","journal-title":"BMC Vet Res"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"e0154934","DOI":"10.1371\/journal.pone.0154934","article-title":"Type of inflammation differentially affects expression of interleukin 1\u03b2 and 6, tumor necrosis factor-\u03b1 and toll-like receptors in subclinical endometritis in mares","volume":"11","author":"Siemieniuch","year":"2016","journal-title":"PLoS One"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/s41584-019-0324-5","article-title":"Evasion of apoptosis by myofibroblasts: a hallmark of fibrotic diseases","volume":"16","author":"Hinz","year":"2020","journal-title":"Nat Rev Rheumatol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.3390\/ijms21041432","article-title":"Persistent breeding-induced endometritis in mares\u2014a multifaceted challenge: from clinical aspects to Immunopathogenesis and pathobiology","volume":"21","author":"Canisso","year":"2020","journal-title":"IJMS"},{"key":"ref11","first-page":"723","article-title":"Equine endometrial biopsy","volume":"2","author":"Kenney","year":"1986","journal-title":"Curr Ther Theriogenol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.anireprosci.2008.03.019","article-title":"The equine endometrosis: new insights into the pathogenesis","volume":"111","author":"Hoffmann","year":"2009","journal-title":"Anim Reprod Sci"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.anireprosci.2014.11.001","article-title":"Expression of receptors for ovarian steroids and prostaglandin E2 in the endometrium and myometrium of mares during estrus, diestrus and early pregnancy","volume":"151","author":"Silva","year":"2014","journal-title":"Anim Reprod Sci"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1530\/rep.1.00596","article-title":"Temporal and spatial associations of oestrogen receptor alpha and progesterone receptor in the endometrium of cyclic and early pregnant mares","volume":"130","author":"Hartt","year":"2005","journal-title":"Reproduction"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1210\/er.2002-0005","article-title":"The matrix metalloproteinase system: changes, regulation, and impact throughout the ovarian and uterine reproductive cycle","volume":"24","author":"Curry","year":"2003","journal-title":"Endocr Rev"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s12958-018-0359-5","article-title":"Prostaglandin E2 involvement in mammalian female fertility: ovulation, fertilization, embryo development and early implantation","volume":"16","author":"Niringiyumukiza","year":"2018","journal-title":"Reprod Biol Endocrinol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/j.fertnstert.2004.11.026","article-title":"Reduced progesterone action during endometrial maturation: a potential risk factor for the development of endometriosis","volume":"83","author":"Osteen","year":"2005","journal-title":"Fertil Steril"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1095\/biolreprod.113.109447","article-title":"Impairment of the interleukin system in equine endometrium during the course of Endometrosis","volume":"89","author":"Sz\u00f3stek","year":"2013","journal-title":"Biol Reprod"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1016\/j.theriogenology.2012.03.024","article-title":"mRNA transcription of prostaglandin synthases and their products in the equine endometrium in the course of fibrosis","volume":"78","author":"Sz\u00f3stek","year":"2012","journal-title":"Theriogenology"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"461","DOI":"10.3389\/fphar.2017.00461","article-title":"Targeting TGF-\u03b2 mediated SMAD signaling for the prevention of fibrosis","volume":"8","author":"Walton","year":"2017","journal-title":"Front Pharmacol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.3390\/cells10071596","article-title":"Extracellular vesicles in organ fibrosis: mechanisms, therapies, and diagnostics","volume":"10","author":"Brigstock","year":"2021","journal-title":"Cells"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1186\/s12951-023-01921-3","article-title":"Extracellular vesicles: emerging roles, biomarkers and therapeutic strategies in fibrotic diseases","volume":"21","author":"Zhu","year":"2023","journal-title":"J Nanobiotechnol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s13075-016-0929-x","article-title":"MicroRNAs in fibrosis: opportunities and challenges","volume":"18","author":"O\u2019Reilly","year":"2016","journal-title":"Arthritis Res Ther"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"112132","DOI":"10.1016\/j.biopha.2021.112132","article-title":"Role of miRNA and lncRNAs in organ fibrosis and aging","volume":"143","author":"Ghafouri-Fard","year":"2021","journal-title":"Biomed Pharmacother"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"948959","DOI":"10.3389\/fbioe.2022.948959","article-title":"MicroRNAs in extracellular vesicles: sorting mechanisms, diagnostic value, isolation, and detection technology","volume":"10","author":"Xu","year":"2022","journal-title":"Front Bioeng Biotechnol"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"24783","DOI":"10.3402\/jev.v3.24783","article-title":"Importance of exosome depletion protocols to eliminate functional and RNA-containing extracellular vesicles from fetal bovine serum","volume":"3","author":"Shelke","year":"2014","journal-title":"J Extracel Ves"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.jim.2009.03.018","article-title":"Improved semiquantitative Western blot technique with increased quantification range","volume":"345","author":"Heidebrecht","year":"2009","journal-title":"J Immunol Methods"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1333883","DOI":"10.1080\/20013078.2017.1333883","article-title":"High throughput nanoparticle tracking analysis for monitoring outer membrane vesicle production","volume":"6","author":"Gerritzen","year":"2017","journal-title":"J Extracel Ves"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1261\/rna.5248604","article-title":"Fast and effective prediction of microRNA\/target duplexes","volume":"10","author":"Rehmsmeier","year":"2004","journal-title":"RNA"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"625","DOI":"10.3390\/ani10040625","article-title":"The healthy and diseased equine endometrium: a review of morphological features and molecular analyses","volume":"10","author":"Sch\u00f6niger","year":"2020","journal-title":"Animals"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/S0165-2427(03)00137-5","article-title":"Endometrial IL-1\u03b2, IL-6 and TNF-\u03b1, mRNA expression in mares resistant or susceptible to post-breeding endometritis","volume":"96","author":"Fumuso","year":"2003","journal-title":"Vet Immunol Immunopathol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1111\/rda.12397","article-title":"Physiopathologic mechanisms involved in Mare Endometrosis","volume":"49","author":"Rebord\u00e3o","year":"2014","journal-title":"Reprod Dom Anim"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"2901","DOI":"10.3390\/ijms24032901","article-title":"The role of NF-\u03baB in endometrial diseases in humans and animals: a review","volume":"24","author":"Zdrojkowski","year":"2023","journal-title":"IJMS"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5772\/intechopen.100515","article-title":"Endometriosis in Mare; what the Mare can teach us when dealing with endometriosis in the woman","volume-title":"Endometriosis \u2013 recent advances, new perspectives and treatments","author":"Trundell D","year":"2022"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"228","DOI":"10.2746\/042516400776563554","article-title":"Cyclical endometrial steroid hormone receptor expression and proliferation intensity in the mare","volume":"32","author":"Aupperle","year":"2010","journal-title":"Equine Vet J"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.theriogenology.2018.10.005","article-title":"Effect of transforming growth factor -\u03b21 on \u03b1-smooth muscle actin and collagen expression in equine endometrial fibroblasts","volume":"124","author":"Sz\u00f3stek-Mioduchowska","year":"2019","journal-title":"Theriogenology"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/nri3819","article-title":"The role of sex hormones in immune protection of the female reproductive tract","volume":"15","author":"Wira","year":"2015","journal-title":"Nat Rev Immunol"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1058862","DOI":"10.3389\/fimmu.2022.1058862","article-title":"Essential immune functions of fibroblasts in innate host defense","volume":"13","author":"Cavagnero","year":"2022","journal-title":"Front Immunol"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1111\/rda.12915","article-title":"Establishment and characterization of a coculture system of equine endometrial epithelial and stromal cells","volume":"52","author":"Lapko","year":"2017","journal-title":"Reprod Dom Anim"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/0093-691X(85)90028-7","article-title":"Serum estradiol-17\u03b2 concentrations during spontaneous silent estrus and after prostaglandin treatment in the mare","volume":"23","author":"Nelson","year":"1985","journal-title":"Theriogenology"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1146\/annurev-pathol-121808-102144","article-title":"The senescence-associated secretory phenotype: the dark side of tumor suppression","volume":"5","author":"Copp\u00e9","year":"2010","journal-title":"Annu Rev Pathol Mech Dis"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.cell.2005.11.003","article-title":"Slugging it out: fine tuning the p53-PUMA death connection","volume":"123","author":"Zilfou","year":"2005","journal-title":"Cells"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"4875","DOI":"10.1091\/mbc.e08-05-0506","article-title":"Snail and Slug promote epithelial-mesenchymal transition through beta-catenin-T-cell factor-4-dependent expression of transforming growth factor-beta3","volume":"19","author":"Medici","year":"2008","journal-title":"Mol Biol Cell"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"6721","DOI":"10.1002\/jcp.27418","article-title":"Slug mediates myofibroblastic differentiation to promote fibrogenesis in buccal mucosa","volume":"234","author":"Fang","year":"2019","journal-title":"Journal Cellular Physiology"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"3151","DOI":"10.3390\/ani11113151","article-title":"Equine Endometrosis pathological features: are they dependent on NF-\u03baB signaling pathway?","volume":"11","author":"Jasi\u0144ski","year":"2021","journal-title":"Animals"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"5405","DOI":"10.7150\/ijbs.75876","article-title":"The role of IL-6 in fibrotic diseases: molecular and cellular mechanisms","volume":"18","author":"Li","year":"2022","journal-title":"Int J Biol Sci"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"582211","DOI":"10.3389\/fvets.2020.582211","article-title":"The inhibition of Cathepsin G on endometrial explants with Endometrosis in the Mare","volume":"7","author":"Amaral","year":"2020","journal-title":"Front Vet Sci"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"2080","DOI":"10.1182\/blood.V94.6.2080","article-title":"Interleukin-6 regulation of matrix metalloproteinase (MMP-2 and MMP-9) and tissue inhibitor of metalloproteinase (TIMP-1) expression in malignant non-Hodgkin\u2019s lymphomas","volume":"94","author":"Kossakowska","year":"1999","journal-title":"Blood"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"349","DOI":"10.4049\/jimmunol.1301906","article-title":"IL-6\u2013mediated induction of matrix Metalloproteinase-9 is modulated by JAK-dependent IL-10 expression in macrophages","volume":"192","author":"Kothari","year":"2014","journal-title":"J Immunol"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1080\/019021490944232","article-title":"Matrix metalloproteinase-2 (MMP-2) and MMP-9 in pulmonary pathology","volume":"31","author":"Chakrabarti","year":"2005","journal-title":"Exp Lung Res"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/1755-1536-4-22","article-title":"Assessment of proteolytic degradation of the basement membrane: a fragment of type IV collagen as a biochemical marker for liver fibrosis","volume":"4","author":"Veidal","year":"2011","journal-title":"Fibrogenesis Tissue Repair"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1002\/bip.10201","article-title":"Matrix metalloproteinases and collagen catabolism","volume":"66","author":"Lauer-Fields","year":"2002","journal-title":"Biopolymers"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.bbrc.2011.02.012","article-title":"Cholestatic liver fibrosis and toxin-induced fibrosis are exacerbated in matrix metalloproteinase-2 deficient mice","volume":"406","author":"Onozuka","year":"2011","journal-title":"Biochem Biophys Res Commun"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1007\/s10620-010-1296-0","article-title":"Loss of matrix metalloproteinase-2 amplifies murine toxin-induced liver fibrosis by upregulating collagen I expression","volume":"56","author":"Radbill","year":"2011","journal-title":"Dig Dis Sci"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"154767","DOI":"10.1016\/j.cyto.2019.154767","article-title":"Effect of proinflammatory cytokines on endometrial collagen and metallopeptidase expression during the course of equine endometrosis","volume":"123","author":"Sz\u00f3stek-Mioduchowska","year":"2019","journal-title":"Cytokine"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"547","DOI":"10.2478\/pjvs-2014-0083","article-title":"Endometrosis \u2013 significance for horse reproduction, pathogenesis, diagnosis, and proposed therapeutic methods","volume":"17","author":"Buczkowska","year":"2014","journal-title":"Pol J Vet Sci"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1071\/RD12153","article-title":"Effect of cytokines and ovarian steroids on equine endometrial function: an in vitro study","volume":"25","author":"Galv\u00e3o","year":"2013","journal-title":"Reprod Fertil Dev"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"599","DOI":"10.4236\/abb.2013.44078","article-title":"Collagen types in relation to expression of estradiol and progesterone receptors in equine endometrial fibrosis","volume":"4","author":"Lunelli","year":"2013","journal-title":"ABB"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1186\/s12974-020-01998-9","article-title":"The peri-menopause in a woman\u2019s life: a systemic inflammatory phase that enables later neurodegenerative disease","volume":"17","author":"McCarthy","year":"2020","journal-title":"J Neuroinflammation"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"297","DOI":"10.31887\/DCNS.2009.11.3\/pmwise","article-title":"Estradiol: a hormone with diverse and contradictory neuroprotective actions","volume":"11","author":"Wise","year":"2009","journal-title":"Dialogues Clin Neurosci"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"615917","DOI":"10.1155\/2014\/615917","article-title":"Estrogen signaling in metabolic inflammation","volume":"2014","author":"Monteiro","year":"2014","journal-title":"Mediat Inflamm"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"8786","DOI":"10.1038\/ncomms9786","article-title":"Propagation of oestrogen receptor-positive and oestrogen-responsive normal human breast cells in culture","volume":"6","author":"Fridriksdottir","year":"2015","journal-title":"Nat Commun"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1186\/s12931-018-0861-5","article-title":"Transforming growth factor beta1 targets estrogen receptor signaling in bronchial epithelial cells","volume":"19","author":"Smith","year":"2018","journal-title":"Respir Res"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"L645","DOI":"10.1152\/ajplung.00176.2011","article-title":"Prostaglandin E protects murine lungs from bleomycin-induced pulmonary fibrosis and lung dysfunction","volume":"301","author":"Dackor","year":"2011","journal-title":"Am J Phys Lung Cell Mol Phys"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"789","DOI":"10.3390\/biom11060789","article-title":"The roles of various prostaglandins in fibrosis: a review","volume":"11","author":"Li","year":"2021","journal-title":"Biomol Ther"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.theriogenology.2020.04.040","article-title":"Prostaglandins effect on matrix metallopeptidases and collagen in mare endometrial fibroblasts","volume":"153","author":"Sz\u00f3stek-Mioduchowska","year":"2020","journal-title":"Theriogenology"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"e0200661","DOI":"10.1371\/journal.pone.0200661","article-title":"Effect of progesterone on Smad signaling and TGF-\u03b2\/Smad-regulated genes in lung epithelial cells","volume":"13","author":"Kunzmann","year":"2018","journal-title":"PLoS One"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1186\/s12958-015-0111-3","article-title":"In vitro progesterone modulation on bacterial endotoxin-induced production of IL-1\u03b2, TNF\u03b1, IL-6, IL-8, IL-10, MIP-1\u03b1, and MMP-9 in pre-labor human term placenta","volume":"13","author":"Garcia-Ru\u00edz","year":"2015","journal-title":"Reprod Biol Endocrinol"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"6217","DOI":"10.1074\/jbc.271.11.6217","article-title":"Negative interaction between the RelA(p65) subunit of NF-\u03baB and the progesterone receptor","volume":"271","author":"Kalkhoven","year":"1996","journal-title":"J Biol Chem"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.3390\/biom12091299","article-title":"Progesterone as an anti-inflammatory drug and Immunomodulator: new aspects in hormonal regulation of the inflammation","volume":"12","author":"Fedotcheva","year":"2022","journal-title":"Biomol Ther"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"130","DOI":"10.2174\/1874312901206010130","article-title":"Role of MicroRNAs in fibrosis","volume":"6","author":"Vettori","year":"2012","journal-title":"TORJ"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"15479","DOI":"10.3390\/ijms232415479","article-title":"The role of microRNAs in inflammation","volume":"23","author":"Das","year":"2022","journal-title":"IJMS"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"2527","DOI":"10.3390\/ijms18122527","article-title":"Role of MicroRNAs in TGF-\u03b2 signaling pathway-mediated pulmonary fibrosis","volume":"18","author":"Kang","year":"2017","journal-title":"IJMS"},{"key":"ref75","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2015.00050","article-title":"MicroRNAs in renal fibrosis","volume":"6","author":"Chung","year":"2015","journal-title":"Front Physiol"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"7660","DOI":"10.1111\/jcmm.16603","article-title":"METTL3\/N6-methyladenosine\/ miR-21-5p promotes obstructive renal fibrosis by regulating inflammation through SPRY1\/ERK\/NF-\u03baB pathway activation","volume":"25","author":"Liu","year":"2021","journal-title":"J Cell Mol Med"},{"key":"ref77","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s13046-018-0965-2","article-title":"Hepatocellular carcinoma-derived exosomal miRNA-21 contributes to tumor progression by converting hepatocyte stellate cells to cancer-associated fibroblasts","volume":"37","author":"Zhou","year":"2018","journal-title":"J Exp Clin Cancer Res"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1038\/labinvest.2015.58","article-title":"MicroRNA-17-5p activates hepatic stellate cells through targeting of Smad7","volume":"95","author":"Yu","year":"2015","journal-title":"Lab Investig"},{"key":"ref79","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1016\/j.bbadis.2012.09.014","article-title":"Cytokine mediated tissue fibrosis","volume":"1832","author":"Borthwick","year":"2013","journal-title":"Biochim Biophys Acta (BBA) - Mol Basis Dis"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"155","DOI":"10.3892\/etm.2018.6160","article-title":"Inhibition of prostaglandin E2 protects abdominal aortic aneurysm from expansion through regulating miR-29b-mediated fibrotic ECM expression","volume":"16","author":"Han","year":"2018","journal-title":"Exp Ther Med"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"2514","DOI":"10.1096\/fj.201801349RR","article-title":"Prostaglandin E2 secreted by mesenchymal stem cells protects against acute liver failure via enhancing hepatocyte proliferation","volume":"33","author":"Liu","year":"2019","journal-title":"FASEB J"},{"key":"ref82","doi-asserted-by":"publisher","first-page":"L1050","DOI":"10.1152\/ajplung.00252.2016","article-title":"MicroRNA-29c regulates apoptosis sensitivity via modulation of the cell-surface death receptor, Fas, in lung fibroblasts","volume":"311","author":"Matsushima","year":"2016","journal-title":"Am J Phys Lung Cell Mol Phys"},{"key":"ref83","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1681\/ASN.2011010055","article-title":"Suppression of microRNA-29 expression by TGF-\u03b21 promotes collagen expression and renal fibrosis","volume":"23","author":"Wang","year":"2012","journal-title":"J Am Soc Nephrol"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"e0244065","DOI":"10.1371\/journal.pone.0244065","article-title":"A strategic expression method of miR-29b and its anti-fibrotic effect based on RNA-sequencing analysis","volume":"15","author":"Fan","year":"2020","journal-title":"PLoS One"},{"key":"ref85","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1177\/1933719118768687","article-title":"Progesterone-induced miR-145\/miR-143 inhibits the proliferation of endometrial epithelial cells","volume":"26","author":"Yuan","year":"2019","journal-title":"Reprod Sci"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"10431","DOI":"10.3390\/ijms221910431","article-title":"PPAR\u03b3 and TGF\u03b2\u2014major regulators of metabolism, inflammation, and fibrosis in the lungs and kidneys","volume":"22","author":"K\u00f6k\u00e9ny","year":"2021","journal-title":"IJMS"},{"key":"ref87","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1111\/ijd.15388","article-title":"Pharmacological activation of PPAR-\u03b3: a potential therapy for skin fibrosis","volume":"60","author":"Ghosh","year":"2021","journal-title":"Int J Dermatol"},{"key":"ref88","doi-asserted-by":"publisher","first-page":"2565","DOI":"10.7150\/thno.22878","article-title":"MicroRNA-378 suppresses myocardial fibrosis through a paracrine mechanism at the early stage of cardiac hypertrophy following mechanical stress","volume":"8","author":"Yuan","year":"2018","journal-title":"Theranostics"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"4398","DOI":"10.26355\/eurrev_201905_17947","article-title":"MicroRNA-378 attenuates myocardial fibrosis by inhibiting MAPK\/ERK pathway","volume":"23","author":"Liu","year":"2019","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.mce.2014.07.022","article-title":"Progesterone receptor expression in granulosa cells is suppressed by microRNA-378-3p","volume":"399","author":"Toms","year":"2015","journal-title":"Mol Cell Endocrinol"},{"key":"ref91","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/j.cmet.2010.09.002","article-title":"miR-378 \u2217 mediates metabolic shift in breast Cancer cells via the PGC-1\u03b2\/ERR\u03b3 transcriptional pathway","volume":"12","author":"Eichner","year":"2010","journal-title":"Cell Metab"},{"key":"ref92","doi-asserted-by":"publisher","first-page":"4766","DOI":"10.1002\/jcp.29354","article-title":"miR-488 mediates negative regulation of the AKT\/NF-\u03baB pathway by targeting Rac1 in LPS-induced inflammation","volume":"235","author":"Liu","year":"2020","journal-title":"J Cell Physiol"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1007\/s12072-022-10404-w","article-title":"miR-488-5p mitigates hepatic stellate cell activation and hepatic fibrosis via suppressing TET3 expression","volume":"17","author":"Qiu","year":"2023","journal-title":"Hepatol Int"},{"key":"ref94","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s41232-022-00210-0","article-title":"Extracellular vesicles in idiopathic pulmonary fibrosis: pathogenesis and therapeutics","volume":"42","author":"Fujita","year":"2022","journal-title":"Inflamm Regener"},{"key":"ref95","doi-asserted-by":"publisher","first-page":"151221","DOI":"10.1016\/j.ejcb.2022.151221","article-title":"Tackling the effects of extracellular vesicles in fibrosis","volume":"101","author":"Mart\u00edn-Taboada","year":"2022","journal-title":"Eur J Cell Biol"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1186\/s12974-018-1204-7","article-title":"Inflammation leads to distinct populations of extracellular vesicles from microglia","volume":"15","author":"Yang","year":"2018","journal-title":"J Neuroinflammation"},{"key":"ref97","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.3390\/ijms18061285","article-title":"The ability of extracellular vesicles to induce a pro-inflammatory host response","volume":"18","author":"Van","year":"2017","journal-title":"Int J Mol Sci"},{"key":"ref98","doi-asserted-by":"publisher","first-page":"109613","DOI":"10.1016\/j.celrep.2021.109613","article-title":"Pro-inflammatory \u03b2 cell small extracellular vesicles induce \u03b2 cell failure through activation of the CXCL10\/CXCR3 axis in diabetes","volume":"36","author":"Javeed","year":"2021","journal-title":"Cell Rep"},{"key":"ref99","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1136\/thoraxjnl-2019-214027","article-title":"Increased extracellular vesicles mediate inflammatory signalling in cystic fibrosis","volume":"75","author":"Useckaite","year":"2020","journal-title":"Thorax"},{"key":"ref100","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/s41418-019-0349-y","article-title":"Exosomal miRNA-19b-3p of tubular epithelial cells promotes M1 macrophage activation in kidney injury","volume":"27","author":"Lv","year":"2020","journal-title":"Cell Death Differ"},{"key":"ref101","doi-asserted-by":"publisher","first-page":"1801153","DOI":"10.1080\/20013078.2020.1801153","article-title":"(sub)populations of extracellular vesicles released by TNF-\u03b1 \u2013triggered human endothelial cells promote vascular inflammation and monocyte migration","volume":"9","author":"Hosseinkhani","year":"2020","journal-title":"J Extracel Ves"},{"key":"ref102","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.tcb.2016.11.003","article-title":"Extracellular vesicles: unique intercellular delivery vehicles","volume":"27","author":"Maas","year":"2017","journal-title":"Trends Cell Biol"},{"key":"ref103","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1083\/jcb.201211138","article-title":"Extracellular vesicles: exosomes, microvesicles, and friends","volume":"200","author":"Raposo","year":"2013","journal-title":"J Cell Biol"}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2023.1271240\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T07:11:39Z","timestamp":1696576299000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2023.1271240\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,6]]},"references-count":103,"alternative-id":["10.3389\/fvets.2023.1271240"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2023.1271240","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,6]]},"article-number":"1271240"}}