{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:51:28Z","timestamp":1791388288129,"version":"4.3.3"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["372896\/2023-5"],"award-info":[{"award-number":["372896\/2023-5"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["141080\/2024-8"],"award-info":[{"award-number":["141080\/2024-8"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["140841\/2021-0"],"award-info":[{"award-number":["140841\/2021-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["312111\/2023-1"],"award-info":[{"award-number":["312111\/2023-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["302938\/2020-6"],"award-info":[{"award-number":["302938\/2020-6"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2021\/14140-5"],"award-info":[{"award-number":["2021\/14140-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Reprod. Sci."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The prostate is a hormone-sensitive gland, in which stromal composition is important for epithelial regulation. Fibrotic alterations in the stroma may enhance epithelial imbalance and pre-neoplastic lesions. The purpose of this study was to assess the time-dependent antifibrotic effects of mycophenolate mofetil (MMF) in rat prostate. Male Wistar rats were treated with MMF for 7 or 30 days, and prostate samples were histologically and immunohistochemically examined. Stromal fiber content, hormone receptor expression, and immune cell incidence were analyzed. Collagen III and elastin fibers decreased at 7 days, with increased matrix metalloproteinases 2 expression and reduced androgen receptor in the epithelium, resulting in decreased proliferation and enhanced apoptosis. Collagen I breakdown at 30 days was associated with increased matrix metalloproteinases 13 and reduced smooth muscle area, with increased non-muscular stroma and vascular density. Degranulated mast cells were increased early on, and macrophages at 30 days, reflecting their successive involvement in stromal remodeling. These findings define two time windows of MMF-induced remodeling: initial extracellular matrix disassembly with epithelial influence, and later structural reorganization with vascular and immune components. This study provides relevant information about MMF as a potential tool for the study of antifibrotic response and stroma-epithelium interactions in androgen-dependent organs.<\/jats:p>","DOI":"10.1007\/s43032-026-02221-5","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:57:10Z","timestamp":1791385030000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Stromal Remodeling and Collagen Dynamics under Antifibrotic Conditions in the Rat Prostate"],"prefix":"10.1007","author":[{"given":"Luiz Roberto","family":"Falleiros Junior","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thalles Fernando Rocha","family":"Ruiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitor","family":"Grigio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Bicalho-Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone Jacovaci","family":"Colleta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena Gabriela","family":"de Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luara Jesus","family":"Ferrato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia Simone Leite","family":"Vilamaior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago","family":"da Silveira Antoniassi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u00eds C\u00e9sar Fava","family":"Spessoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0970-4288","authenticated-orcid":false,"given":"Sebasti\u00e3o Roberto","family":"Taboga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Nestor","family":"Facio Junior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"2221_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2025.108867","volume":"133","author":"D Marcoccia","year":"2025","unstructured":"Marcoccia D, Mollari M, Galli FS, Cuva C, Tassinari V, Mantovani A. Prostate as a target of endocrine disrupting chemicals: relevance, pathways, assays. Reprod Toxicol. 2025;133:108867. https:\/\/doi.org\/10.1016\/j.reprotox.2025.108867.","journal-title":"Reprod Toxicol"},{"key":"2221_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13053-025-00310-1","volume":"23","author":"J McHugh","year":"2025","unstructured":"McHugh J, Bancroft E, Kote-Jarai Z, Eeles R. Prostate cancer: genetics in practice now and in the future. Hered Cancer Clin Pract. 2025;23:1\u20134. https:\/\/doi.org\/10.1186\/s13053-025-00310-1.","journal-title":"Hered Cancer Clin Pract"},{"key":"2221_CR3","doi-asserted-by":"publisher","first-page":"205","DOI":"10.2147\/RRU.S477396","volume":"16","author":"G Xu","year":"2024","unstructured":"Xu G, Dai G, Huang Z, Guan Q, Du C, Xu X. The etiology and pathogenesis of benign prostatic hyperplasia: the roles of sex hormones and anatomy. Res Rep Urol. 2024;16:205\u201314. https:\/\/doi.org\/10.2147\/RRU.S477396.","journal-title":"Res Rep Urol"},{"key":"2221_CR4","doi-asserted-by":"publisher","unstructured":"Di Carlo E, Sorrentino C. The multifaceted role of the stroma in the healthy prostate and prostate cancer. J Transl Med. 2024;22. https:\/\/doi.org\/10.1186\/s12967-024-05564-2.","DOI":"10.1186\/s12967-024-05564-2"},{"key":"2221_CR5","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.acthis.2014.10.009","volume":"117","author":"BF Gon\u00e7alves","year":"2015","unstructured":"Gon\u00e7alves BF, d. Campos SGP, Costa CFP, Scarano WR, G\u00f3es RM, Taboga SR. Key participants of the tumor microenvironment of the prostate: an approach of the structural dynamic of cellular elements and extracellular matrix components during epithelial-stromal transition. Acta Histochem. 2015;117:4\u201313. https:\/\/doi.org\/10.1016\/j.acthis.2014.10.009.","journal-title":"Acta Histochem"},{"key":"2221_CR6","doi-asserted-by":"publisher","DOI":"10.1016\/j.acthis.2024.152209","author":"TFR Ruiz","year":"2024","unstructured":"Ruiz TFR, Ferrato LJ, de Souza LG, Brito-Filho GE, Leonel ECR, Taboga SR. The elastic system: a review of elastin-related techniques and hematoxylin-eosin\/phloxine applicability for normal and pathological tissue description. Acta Histochem. 2024. https:\/\/doi.org\/10.1016\/j.acthis.2024.152209.","journal-title":"Acta Histochem"},{"key":"2221_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2025.104954","volume":"141","author":"A Sato","year":"2025","unstructured":"Sato A, Takagi K, Yamaguchi-Tanaka M, Okushima J, Yamazaki Y, Ito A, et al. Matrix metalloproteinase-3 is a potent prognostic factor associated with cell proliferation and migration in prostate cancer. Exp Mol Pathol. 2025;141:104954. https:\/\/doi.org\/10.1016\/j.yexmp.2025.104954.","journal-title":"Exp Mol Pathol"},{"key":"2221_CR8","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24087022","volume":"24","author":"N Eiro","year":"2023","unstructured":"Eiro N, Medina A, Gonzalez LO, Fraile M, Palacios A, Escaf S, et al. Evaluation of matrix metalloproteases by artificial intelligence techniques in negative biopsies as new diagnostic strategy in prostate cancer. Int J Mol Sci. 2023;24:7022. https:\/\/doi.org\/10.3390\/ijms24087022.","journal-title":"Int J Mol Sci"},{"key":"2221_CR9","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1212585","author":"ED Czyrnik","year":"2023","unstructured":"Czyrnik ED, Wieseh\u00f6fer M, Dankert JT, Wach S, Wagner M, Spahn M, et al. Stromal-epithelial interaction induces GALNT14 in prostate carcinoma cells. Front Oncol. 2023. https:\/\/doi.org\/10.3389\/fonc.2023.1212585.","journal-title":"Front Oncol"},{"key":"2221_CR10","doi-asserted-by":"publisher","DOI":"10.1002\/pros.24824","author":"EP J\u00fanior","year":"2024","unstructured":"J\u00fanior EP, d. A. Gomes EF, de Lima MFR, Raimundo JVS, Marinho ML, Soares YVC, et al. Reactive stroma and acinar morphology in prostate cancer: implications for progression and prognostic assessment. Prostate. 2024. https:\/\/doi.org\/10.1002\/pros.24824.","journal-title":"Prostate"},{"key":"2221_CR11","doi-asserted-by":"publisher","first-page":"3215","DOI":"10.3390\/cancers16183215","volume":"16","author":"D Vecchiotti","year":"2024","unstructured":"Vecchiotti D, Clementi L, Cornacchia E, Di Vito Nolfi M, Verzella D, Capece D, et al. Evidence of the link between stroma remodeling and prostate cancer prognosis. Cancers (Basel). 2024;16:3215. https:\/\/doi.org\/10.3390\/cancers16183215.","journal-title":"Cancers (Basel)"},{"key":"2221_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/adhm.202203076","volume":"12","author":"W Wang","year":"2023","unstructured":"Wang W, Xiao D, Lin L, Gao X, Peng L, Chen J, et al. Antifibrotic effects of tetrahedral framework nucleic acids by inhibiting macrophage polarization and macrophage-myofibroblast transition in bladder remodeling. Adv Healthc Mater. 2023;12:1\u201313. https:\/\/doi.org\/10.1002\/adhm.202203076.","journal-title":"Adv Healthc Mater"},{"key":"2221_CR13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/plants14071150","volume":"14","author":"H Horita","year":"2025","unstructured":"Horita H, Tsukiboshi Y, Ogata K, Ogata A, Kurita H, Yamashita S, et al. Sasa veitchii extract mitigates mycophenolate mofetil-induced human palatal cell proliferation inhibition by downregulating microRNA-4680-3p. Plants. 2025;14:1\u201314. https:\/\/doi.org\/10.3390\/plants14071150.","journal-title":"Plants"},{"key":"2221_CR14","doi-asserted-by":"publisher","first-page":"10715","DOI":"10.3748\/wjg.v20.i31.10715","volume":"20","author":"H Chen","year":"2014","unstructured":"Chen H, Chen B. Clinical mycophenolic acid monitoring in liver transplant recipients. World J Gastroenterol. 2014;20:10715\u201328. https:\/\/doi.org\/10.3748\/wjg.v20.i31.10715.","journal-title":"World J Gastroenterol"},{"key":"2221_CR15","doi-asserted-by":"publisher","first-page":"1786","DOI":"10.1111\/j.1600-6143.2008.02322.x","volume":"8","author":"C Morath","year":"2008","unstructured":"Morath C, Reuter H, Simon V, Krautkramer E, Muranyi W, Schwenger V, et al. Effects of mycophenolic acid on human fibroblast proliferation, migration and adhesion in vitro and in vivo. Am J Transplant. 2008;8:1786\u201397. https:\/\/doi.org\/10.1111\/j.1600-6143.2008.02322.x.","journal-title":"Am J Transplant"},{"key":"2221_CR16","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1124\/jpet.106.117051","volume":"321","author":"N Roos","year":"2007","unstructured":"Roos N, Poulalhon N, Farge D, Madelaine I, Mauviel A, Verrecchia F. In vitro evidence for a direct antifibrotic role of the immunosuppressive drug mycophenolate mofetil. J Pharmacol Exp Ther. 2007;321:583\u20139. https:\/\/doi.org\/10.1124\/jpet.106.117051.","journal-title":"J Pharmacol Exp Ther"},{"key":"2221_CR17","doi-asserted-by":"publisher","first-page":"4614","DOI":"10.3390\/ijerph17124614","volume":"17","author":"M Grabowska","year":"2020","unstructured":"Grabowska M, Laszczy\u0144ska M, K\u0119dzierska-Kapuza K, Kram A, Gill K, Piasecka M. The effects of long-term immunosuppressive therapies on the structure of the rat prostate. Int J Environ Res Public Health. 2020;17:4614. https:\/\/doi.org\/10.3390\/ijerph17124614.","journal-title":"Int J Environ Res Public Health"},{"key":"2221_CR18","doi-asserted-by":"publisher","first-page":"2899","DOI":"10.2147\/DDDT.S111695","volume":"10","author":"M Grabowska","year":"2016","unstructured":"Grabowska M, K\u0119dzierska K, Michaek K, S\u0142uczanowska-G\u0142abowska S, Grabowski M, Piasecka M, et al. Effects of an immunosuppressive treatment on the rat prostate. Drug Des Devel Ther. 2016;10:2899\u2013915. https:\/\/doi.org\/10.2147\/DDDT.S111695.","journal-title":"Drug Des Devel Ther"},{"key":"2221_CR19","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1038\/s41443-019-0138-7","volume":"32","author":"T Antoniassi","year":"2020","unstructured":"Antoniassi T, J\u00fanior FNF, Spessoto LCF, Guerra LH, Campos SS, Taboga S. Anti-fibrotic effect of mycophenolate mofetil on Peyronie\u2019s disease experimentally induced with TGF-\u03b2. Int J Impot Res. 2020;32:201\u20136. https:\/\/doi.org\/10.1038\/s41443-019-0138-7.","journal-title":"Int J Impot Res"},{"key":"2221_CR20","first-page":"131","volume":"12","author":"ER Weibel","year":"1978","unstructured":"Weibel ER. Principles and methods for the morphometric study of the lung and other organs. Lab Invest. 1978;12:131\u201355.","journal-title":"Lab Invest"},{"key":"2221_CR21","doi-asserted-by":"publisher","first-page":"2270","DOI":"10.1158\/0008-5472.can-03-0946","volume":"64","author":"SB Shappell","year":"2004","unstructured":"Shappell SB, Thomas GV, Roberts RL, Herbert R, Ittmann MM, Rubin MA, et al. Prostate pathology of genetically engineered mice: definitions and classification. The consensus report from the Bar Harbor meeting of the Mouse Models of Human Cancer Consortium Prostate Pathology Committee. Cancer Res. 2004;64:2270\u2013305. https:\/\/doi.org\/10.1158\/0008-5472.can-03-0946.","journal-title":"Cancer Res"},{"key":"2221_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5","volume":"7","author":"P Bankhead","year":"2017","unstructured":"Bankhead P, Loughrey MB, Fern\u00e1ndez JA, Dombrowski Y, McArt DG, Dunne PD, et al. QuPath: open source software for digital pathology image analysis. Sci Rep. 2017;7:16878. https:\/\/doi.org\/10.1038\/s41598-017-17204-5.","journal-title":"Sci Rep"},{"key":"2221_CR23","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1679\/aohc.67.417","volume":"67","author":"GR Cunha","year":"2004","unstructured":"Cunha GR, Cooke PS, Kurita T. Role of stromal-epithelial interactions in hormonal responses. Arch Histol Cytol. 2004;67:417\u201334. https:\/\/doi.org\/10.1679\/aohc.67.417.","journal-title":"Arch Histol Cytol"},{"key":"2221_CR24","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-14-0138","author":"CM Nieto","year":"2014","unstructured":"Nieto CM, Rider LC, Cramer SD. Influence of stromal-epithelial interactions on androgen action. Endocr Relat Cancer. 2014. https:\/\/doi.org\/10.1530\/ERC-14-0138.","journal-title":"Endocr Relat Cancer"},{"key":"2221_CR25","first-page":"101","volume":"20","author":"P Vilamaior","year":"2003","unstructured":"Vilamaior P, Suzigan S, Carvalho H, Taboga S. Structural characterization and distribution of elastic system fibers in the human prostate and some prostatic lesions. Braz J Morphol Sci. 2003;20:101\u20137.","journal-title":"Braz J Morphol Sci"},{"key":"2221_CR26","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1002\/1097-0045(20001101)45:3<253::aid-pros8>3.0.co;2-p","volume":"45","author":"PS Vilamaior","year":"2000","unstructured":"Vilamaior PS, Felisbino SL, Taboga SR, Carvalho HF. Collagen fiber reorganization in the rat ventral prostate following androgen deprivation: a possible role for smooth muscle cells. Prostate. 2000;45:253\u20138. https:\/\/doi.org\/10.1002\/1097-0045(20001101)45:3%3c253::aid-pros8%3e3.0.co;2-p.","journal-title":"Prostate"},{"key":"2221_CR27","doi-asserted-by":"publisher","first-page":"305","DOI":"10.4103\/1008-682X.122582","volume":"16","author":"J Tang","year":"2014","unstructured":"Tang J, Zhang Y, Zhang MB, Li YM, Fei X, Song ZG. Tissue elasticity displayed by elastography and its correlation with the characteristics of collagen type I and type III in prostatic stroma. Asian J Androl. 2014;16:305\u20138. https:\/\/doi.org\/10.4103\/1008-682X.122582.","journal-title":"Asian J Androl"},{"key":"2221_CR28","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2020.101458","volume":"68","author":"MA Flamini","year":"2021","unstructured":"Flamini MA, Barbeito CG, D\u00edaz AO, Portiansky EL. Comparison of the structural and ultrastructural characteristics of the female prostate between pregnant and non-pregnant plains viscacha (Lagostomus maximus). Tissue Cell. 2021;68:101458. https:\/\/doi.org\/10.1016\/j.tice.2020.101458.","journal-title":"Tissue Cell"},{"key":"2221_CR29","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1038\/aja.2008.39","volume":"11","author":"YN Niu","year":"2009","unstructured":"Niu YN, Xia SJ. Stroma-epithelium crosstalk in prostate cancer, Asian. J Androl. 2009;11:28\u201335. https:\/\/doi.org\/10.1038\/aja.2008.39.","journal-title":"J Androl"},{"key":"2221_CR30","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010711","author":"A Kader","year":"2023","unstructured":"Kader A, Kaufmann JO, Mangarova DB, Moeckel J, Adams LC, Brangsch J, et al. Collagen-specific molecular magnetic resonance imaging of prostate cancer. Int J Mol Sci. 2023. https:\/\/doi.org\/10.3390\/ijms24010711.","journal-title":"Int J Mol Sci"},{"key":"2221_CR31","doi-asserted-by":"publisher","first-page":"1915","DOI":"10.7150\/jca.23648","volume":"9","author":"O Zenata","year":"2018","unstructured":"Zenata O, Dvorak Z, Vrzal R. Mycophenolate mofetil induces c-Jun-N-terminal kinase expression in 22Rv1 cells: an impact on androgen receptor signaling. J Cancer. 2018;9:1915\u201324. https:\/\/doi.org\/10.7150\/jca.23648.","journal-title":"J Cancer"},{"key":"2221_CR32","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1111\/j.1399-0012.2006.00597.x","volume":"20","author":"C Morath","year":"2006","unstructured":"Morath C, Schwenger V, Beimler J, Mehrabi A, Schmidt J, Zeier M, et al. Antifibrotic actions of mycophenolic acid. Clin Transplant. 2006;20:25\u20139. https:\/\/doi.org\/10.1111\/j.1399-0012.2006.00597.x.","journal-title":"Clin Transplant"},{"key":"2221_CR33","doi-asserted-by":"publisher","DOI":"10.1590\/s0102-865020190100000005","volume":"34","author":"CFEM Osorio","year":"2019","unstructured":"Osorio CFEM, Costa WS, Gallo CBM, Sampaio FJB. Expression of stromal elements of prostatic adenocarcinoma in different gleason scores. Acta Cir Bras. 2019;34:e201901005. https:\/\/doi.org\/10.1590\/s0102-865020190100000005.","journal-title":"Acta Cir Bras"},{"key":"2221_CR34","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1006\/cbir.1996.0104","volume":"20","author":"HF De Carvalho","year":"1996","unstructured":"De Carvalho HF, Line SRP. Basement membrane associated changes in the rat ventral prostate following castration. Cell Biol Int. 1996;20:809\u201319. https:\/\/doi.org\/10.1006\/cbir.1996.0104.","journal-title":"Cell Biol Int"},{"key":"2221_CR35","doi-asserted-by":"publisher","first-page":"241","DOI":"10.3892\/br.2015.553","volume":"4","author":"T Xie","year":"2016","unstructured":"Xie T, Dong B, Yan Y, Hu G, Xu Y. Association between MMP-2 expression and prostate cancer: a meta-analysis. Biomed Rep. 2016;4:241\u20135. https:\/\/doi.org\/10.3892\/br.2015.553.","journal-title":"Biomed Rep"},{"key":"2221_CR36","doi-asserted-by":"publisher","first-page":"3704","DOI":"10.1111\/febs.15899","volume":"289","author":"CEH Schmelzer","year":"2022","unstructured":"Schmelzer CEH, Duca L. Elastic fibers: formation, function, and fate during aging and disease. FEBS J. 2022;289:3704\u201330. https:\/\/doi.org\/10.1111\/febs.15899.","journal-title":"FEBS J"},{"key":"2221_CR37","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1016\/j.bbrc.2017.10.022","volume":"493","author":"SAA dos Santos","year":"2017","unstructured":"dos Santos SAA, Porto Amorim EM, Ribeiro LM, Rinaldi JC, Delella FK, Justulin LA, et al. Hyperglycemic condition during puberty increases collagen fibers deposition in the prostatic stroma and reduces MMP-2 activity. Biochem Biophys Res Commun. 2017;493:1581\u20136. https:\/\/doi.org\/10.1016\/j.bbrc.2017.10.022.","journal-title":"Biochem Biophys Res Commun"},{"key":"2221_CR38","first-page":"2912","volume":"8","author":"JA Tuxhorn","year":"2002","unstructured":"Tuxhorn JA, Ayala GE, Smith MJ, Smith VC, Dang TD, Rowley DR. Reactive stroma in human prostate cancer: induction of myofibroblast phenotype and extracellular matrix remodeling Clin. Cancer Res. 2002;8:2912\u201323.","journal-title":"Cancer Res"},{"key":"2221_CR39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/BIOMEDICINES8070221","volume":"8","author":"D Lauritano","year":"2020","unstructured":"Lauritano D, Moreo G, Limongelli L, Palmieri A, Carinci F. Drug-induced gingival overgrowth: the effect of cyclosporin a and mycophenolate mophetil on human gingival fibroblasts. Biomedicines. 2020;8:1\u201312. https:\/\/doi.org\/10.3390\/BIOMEDICINES8070221.","journal-title":"Biomedicines"},{"key":"2221_CR40","doi-asserted-by":"publisher","first-page":"2691","DOI":"10.1158\/0008-5472.CAN-05-2919","volume":"66","author":"L Blavier","year":"2006","unstructured":"Blavier L, Lazaryev A, Dorey F, Shackleford GM, DeClerck YA. Matrix metalloproteinases play an active role in Wnt1-induced mammary tumorigenesis. Cancer Res. 2006;66:2691\u20139. https:\/\/doi.org\/10.1158\/0008-5472.CAN-05-2919.","journal-title":"Cancer Res"},{"key":"2221_CR41","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1507\/endocrj.K07-009","volume":"54","author":"F Shidaifat","year":"2007","unstructured":"Shidaifat F, Gharaibeh M, Bani-Ismail Z. Effect of castration on extracellular matrix remodeling and angiogenesis of the prostate gland. Endocr J. 2007;54:521\u20139. https:\/\/doi.org\/10.1507\/endocrj.K07-009.","journal-title":"Endocr J"},{"key":"2221_CR42","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1007\/s12016-023-08963-3","volume":"65","author":"R Bhat","year":"2023","unstructured":"Bhat R, Tonutti A, Timilsina S, Selmi C, Gershwin ME. Perspectives on mycophenolate mofetil in the management of autoimmunity. Clin Rev Allergy Immunol. 2023;65:86\u2013100. https:\/\/doi.org\/10.1007\/s12016-023-08963-3.","journal-title":"Clin Rev Allergy Immunol"},{"key":"2221_CR43","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1111\/j.1529-8019.2007.00136.x","volume":"20","author":"J Zwerner","year":"2007","unstructured":"Zwerner J, Fiorentino D. Mycophenolate mofetil. Dermatol Ther. 2007;20:229\u201338. https:\/\/doi.org\/10.1111\/j.1529-8019.2007.00136.x.","journal-title":"Dermatol Ther"},{"key":"2221_CR44","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1158\/0008-5472.CAN-11-0943","volume":"72","author":"S Shah","year":"2012","unstructured":"Shah S, Prasad S, Knudsen KE. Targeting pioneering factor and hormone receptor cooperative pathways to suppress tumor progression. Cancer Res. 2012;72:1248\u201359. https:\/\/doi.org\/10.1158\/0008-5472.CAN-11-0943.","journal-title":"Cancer Res"},{"key":"2221_CR45","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1038\/ni.2109","volume":"12","author":"SJ Galli","year":"2011","unstructured":"Galli SJ, Borregaard N, Wynn TA. Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils. Nat Immunol. 2011;12:1035\u201344. https:\/\/doi.org\/10.1038\/ni.2109.","journal-title":"Nat Immunol"},{"key":"2221_CR46","doi-asserted-by":"publisher","unstructured":"Gonzalez-Avila G, Sommer B, Garc\u00eda-Hern\u00e1ndez AA, Ramos C. Matrix metalloproteinases\u2019 role in tumor microenvironment. 2020. https:\/\/doi.org\/10.1007\/978-3-030-40146-7_5.","DOI":"10.1007\/978-3-030-40146-7_5"},{"key":"2221_CR47","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.3892\/mmr.2017.6215","volume":"15","author":"L Xu","year":"2017","unstructured":"Xu L, Cai Z, Yang F, Chen M. Activation-induced upregulation of MMP9 in mast cells is a positive feedback mediator for mast cell activation. Mol Med Rep. 2017;15:1759\u201364. https:\/\/doi.org\/10.3892\/mmr.2017.6215.","journal-title":"Mol Med Rep"},{"key":"2221_CR48","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1007\/s10585-012-9473-5","volume":"29","author":"M Zollo","year":"2012","unstructured":"Zollo M, Di Dato V, Spano D, De Martino D, Liguori L, Marino N, et al. Targeting monocyte chemotactic protein-1 synthesis with bindarit induces tumor regression in prostate and breast cancer animal models. Clin Exp Metastasis. 2012;29:585\u2013601. https:\/\/doi.org\/10.1007\/s10585-012-9473-5.","journal-title":"Clin Exp Metastasis"},{"key":"2221_CR49","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.immuni.2016.02.015","volume":"44","author":"TA Wynn","year":"2016","unstructured":"Wynn TA, Vannella KM. Macrophages in tissue repair, regeneration, and fibrosis. Immunity. 2016;44:450\u201362. https:\/\/doi.org\/10.1016\/j.immuni.2016.02.015.","journal-title":"Immunity"},{"key":"2221_CR50","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-022-00856-w","author":"X Zhao","year":"2022","unstructured":"Zhao X, Chen J, Sun H, Zhang Y, Zou D. New insights into fibrosis from the ECM degradation perspective: the macrophage-MMP-ECM interaction. Cell Biosci. 2022. https:\/\/doi.org\/10.1186\/s13578-022-00856-w.","journal-title":"Cell Biosci"}],"container-title":["Reproductive Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43032-026-02221-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s43032-026-02221-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43032-026-02221-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:57:12Z","timestamp":1791385032000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s43032-026-02221-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":50,"alternative-id":["2221"],"URL":"https:\/\/doi.org\/10.1007\/s43032-026-02221-5","relation":{},"ISSN":["1933-7191","1933-7205"],"issn-type":[{"value":"1933-7191","type":"print"},{"value":"1933-7205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"assertion":[{"value":"5 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was approved by the Committee for Ethics in the Use of Animals (CEUA) of the Faculty of Medicine of S\u00e3o Jos\u00e9 do Rio Preto (FAMERP) under protocol number 001\u2013003819\/2019.","order":1,"name":"Ethics","label":"Ethics Approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent to Participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":3,"name":"Ethics","label":"Consent for Publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no conflicts of interest.","order":4,"name":"Ethics","label":"Conflicts of Interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}