{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T06:37:54Z","timestamp":1762843074748,"version":"build-2065373602"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Benign prostatic hyperplasia (BPH) is a common age-associated disorder characterized by non-malignant proliferation of prostate tissues. However, its underlying molecular mechanisms remain incompletely elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A rat model of BPH was established via surgical castration followed by testosterone propionate administration. Proteomic profiling was performed on prostate tissues from BPH and sham-operated rats. Public datasets of BPH patients and healthy individuals were also analyzed to validate the translational relevance. In addition, qPCR was conducted on both rat tissues and human-derived prostate cell lines to confirm gene expression levels. Furthermore, immunohistochemistry was performed on prostate tissue samples from BPH patients to examine the expression and localization of the target proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Proteomic analysis revealed significant upregulation of four proteins\u2014QPCT, ARHGEF37, FLNC, and LGALS7\u2014in BPH model rats compared with controls. KEGG pathway enrichment identified the MAPK signaling pathway as a potential key regulator of BPH progression. Similar expression patterns were observed in human datasets. qPCR results further validated the elevated expression of these four genes in both rat and human BPH-related samples. Immunohistochemistry further demonstrated that all four proteins were highly expressed in prostate tissues from BPH patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The aberrant overexpression of QPCT, ARHGEF37, FLNC, and LGALS7, along with dysregulation of the MAPK signaling pathway, may contribute to BPH pathogenesis. These findings provide new insights into the molecular mechanisms of BPH and may inform the development of diagnostic markers or therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1606607","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T06:32:57Z","timestamp":1762842777000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitogen-activated protein kinase pathway and four genes involved in the development of benign prostatic hyperplasia: in vivo and vitro validation"],"prefix":"10.3389","volume":"16","author":[{"given":"Jia-Min","family":"Gu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing-Pei","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu-Yao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tong","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuang-Ying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xian-Tao","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2014.12.038","article-title":"EAU guidelines on the assessment of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction","volume":"67","author":"Gratzke","year":"2015","journal-title":"Eur Urology"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2015.03.035","article-title":"Lower urinary tract symptoms in men: refocus on your patients","volume":"67","author":"Cornu","year":"2015","journal-title":"Eur Urology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s40779-021-00359-8","article-title":"Epidemiological trends of urinary tract infections, urolithiasis and benign prostatic hyperplasia in 203 countries and territories from 1990 to 2019","volume":"8","author":"Zhu","year":"2021","journal-title":"Mil Med Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.23736\/S2724-6051.24.06269-4","article-title":"Ejaculation preservation in BPH: a question of size","volume":"76","author":"Finati","year":"2024","journal-title":"Minerva Urol Nephrol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/aja.2010.89","article-title":"Androgen receptor signaling and mutations in prostate cancer","volume":"12","author":"Koochekpour","year":"2010","journal-title":"Asian J Androl"},{"key":"B6","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s40779-024-00569-w","article-title":"Global burden of benign prostatic hyperplasia, urinary tract infections, urolithiasis, bladder cancer, kidney cancer, and prostate cancer from 1990 to 2021","volume":"11","author":"Zi","year":"2024","journal-title":"Mil Med Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12082784","article-title":"The efficacy of flogofilm\u00ae in the treatment of chronic bacterial prostatitis as an adjuvant to antibiotic therapy: A randomized prospective trial","volume":"12","author":"Barone","year":"2023","journal-title":"J Clin Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2023.04.006","article-title":"Targeting benign prostate hyperplasia treatments: AR\/TGF-\u03b2\/NOX4 inhibition by apocynin suppresses inflammation and proliferation","volume":"57","author":"Jin","year":"2024","journal-title":"J Adv Res"},{"key":"B9","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1038\/s41419-022-04995-3","article-title":"Ellagic acid improves benign prostate hyperplasia by regulating androgen signaling and STAT3","volume":"13","author":"Park","year":"2022","journal-title":"Cell Death Dis"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2133","DOI":"10.1038\/s41467-022-29719-1","article-title":"TNF is a potential therapeutic target to suppress prostatic inflammation and hyperplasia in autoimmune disease","volume":"13","author":"Vickman","year":"2022","journal-title":"Nat Commun"},{"key":"B11","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/sj.cr.7290105","article-title":"MAPK signal pathways in the regulation of cell proliferation in mammalian cells","volume":"12","author":"Zhang","year":"2002","journal-title":"Cell Res"},{"key":"B12","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1038\/s41419-022-04522-4","article-title":"Glucose-regulated protein 78 modulates cell growth, epithelial-mesenchymal transition, and oxidative stress in the hyperplastic prostate","volume":"13","author":"Fu","year":"2022","journal-title":"Cell Death Dis"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118970","article-title":"Hosta plantaginea (Lam.) Aschers flower modulates inflammation and amino acid metabolism by inhibiting NF-\u03baB\/MAPK\/JAK-STAT\/PI3K-Akt and AMPK pathways to alleviate benign prostatic hyperplasia in rats","volume":"337","author":"Wang","year":"2025","journal-title":"J\u00a0Ethnopharmacol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s40779-022-00373-4","article-title":"Alterations of gut microbiota diversity, composition and metabonomics in testosterone-induced benign prostatic hyperplasia rats","volume":"9","author":"Li","year":"2022","journal-title":"Military Med Res"},{"key":"B15","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s40779-024-00533-8","article-title":"P. gingivalis in oral-prostate axis exacerbates benign prostatic hyperplasia via IL-6\/IL-6R pathway","volume":"11","author":"Wang","year":"2024","journal-title":"Military Med Res"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.4103\/aja2021114","article-title":"Combined treatment with dihydrotestosterone and lipopolysaccharide modulates prostate homeostasis by upregulating TNF-\u03b1 from M1 macrophages and promotes proliferation of prostate stromal cells","volume":"24","author":"Tong","year":"2022","journal-title":"Asian J Androl"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/pros.24046","article-title":"Tight junction protein claudin-1 is downregulated by TGF-\u03b21 via MEK signaling in benign prostatic epithelial cells","volume":"80","author":"Wang","year":"2020","journal-title":"Prostate"},{"key":"B18","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1186\/s12967-023-04432-9","article-title":"Glutathione Peroxidase 3 induced mitochondria-mediated apoptosis via AMPK\/ERK1\/2 pathway and resisted autophagy-related ferroptosis via AMPK\/mTOR pathway in hyperplastic prostate","volume":"21","author":"Li","year":"2023","journal-title":"J\u00a0Transl Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.19852\/j.cnki.jtcm.2023.03.003","article-title":"Efficacy of Buzhong Yiqi decoction on benign prostatic hyperplasia and its possible mechanism","volume":"43","author":"Lihua","year":"2023","journal-title":"J Tradit Chin Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2023.103644","article-title":"Therapeutic potential of glutaminyl cyclases: Current status and emerging trends","volume":"28","author":"Coimbra","year":"2023","journal-title":"Drug Discov Today"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c00325","article-title":"Glutaminyl cyclase, diseases, and development of glutaminyl cyclase inhibitors","volume":"64","author":"Xu","year":"2021","journal-title":"J Med Chem"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e202207097","DOI":"10.1083\/jcb.202207097","article-title":"Senescent cells suppress macrophage-mediated corpse removal via upregulation of the CD47-QPCT\/L axis","volume":"222","author":"Schloesser","year":"2022","journal-title":"J Cell Biol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.362","article-title":"Rho guanine nucleotide exchange factors: regulators of Rho GTPase activity in development and disease","volume":"33","author":"Cook","year":"2014","journal-title":"Oncogene"},{"key":"B24","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1186\/s13046-022-02441-y","article-title":"ARHGEF37 overexpression promotes extravasation and metastasis of hepatocellular carcinoma via directly activating Cdc42","volume":"41","author":"Zhang","year":"2022","journal-title":"J Exp Clin Cancer Res"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2025.1535541","article-title":"Identification of diagnostic biomarkers for fibromyalgia using gene expression analysis and machine learning","volume":"16","author":"Zhao","year":"2025","journal-title":"Front Genet"},{"key":"B26","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s00401-012-1054-9","article-title":"Filamin C-related myopathies: pathology and mechanisms","volume":"125","author":"F\u00fcrst","year":"2013","journal-title":"Acta Neuropathol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1016\/j.ijbiomac.2022.11.162","article-title":"Decoding ceRNA regulatory network and autophagy-related genes in benign prostatic hyperplasia","volume":"225","author":"Zhou","year":"2023","journal-title":"Int J Biol Macromol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.105400","article-title":"The universe of galectin-binding partners and their functions in health and disease","volume":"299","author":"Troncoso","year":"2023","journal-title":"J Biol Chem"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5c00071","article-title":"Development of Galectin-7-specific nanobodies: implications for immunotherapy and molecular imaging in cancer","volume":"68","author":"Nehme\u0301","year":"2025","journal-title":"J Med Chem"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090876","article-title":"Overexpression of galectin-7, A myoepithelial cell marker, enhances spontaneous metastasis of breast cancer cells","volume":"176","author":"Demers","year":"2010","journal-title":"Am J Pathology"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.2741\/3937","article-title":"A distinctive role for galectin-7 in cancer","volume":"17","author":"St-Pierre","year":"2012","journal-title":"Front Biosci (Landmark Ed)"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1172\/JCI130740","article-title":"Galectin-7 downregulation in lesional keratinocytes contributes to enhanced IL-17A signaling and skin pathology in psoriasis","volume":"131","author":"Chen","year":"2021","journal-title":"J Clin Invest"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1790","article-title":"siRNA screen identifies QPCT as a druggable target for Huntington\u2019s disease","volume":"11","author":"Jimenez-Sanchez","year":"2015","journal-title":"Nat\u00a0Chem Biol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.4c02247","article-title":"Targeting QPCTL: an emerging therapeutic opportunity","volume":"68","author":"Yu","year":"2025","journal-title":"J Med Chem"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3390\/biom11111720","article-title":"Functions and inhibition of Galectin-7, an\u00a0emerging target in cellular pathophysiology","volume":"11","author":"Sewgobind","year":"2021","journal-title":"Biomolecules"},{"key":"B36","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/s41573-023-00636-2","article-title":"Targeting galectin-driven regulatory circuits in cancer and fibrosis","volume":"22","author":"Mari\u00f1o","year":"2023","journal-title":"Nat Rev Drug Discov"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1606607\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T06:33:03Z","timestamp":1762842783000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1606607\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,11]]},"references-count":36,"alternative-id":["10.3389\/fimmu.2025.1606607"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1606607","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,11]]},"article-number":"1606607"}}