{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T02:24:19Z","timestamp":1750645459391,"version":"3.37.3"},"reference-count":43,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,11,22]],"date-time":"2018-11-22T00:00:00Z","timestamp":1542844800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This study primarily explored how miR\u2010145, mitogen\u2010activated protein kinase (MAPK) signaling and a downstream transcription factor (i.e., SOX9) mediated development of hypospadias. The hypospadias tissues and preputial tissues were isolated from pediatric inpatients postoperatively. Simultaneously, the rat models of hypospadias were established, and spermatogonial stem cells were separated. The expressions of proteins that symbolized cell apoptosis and oxidative stress were quantified via western blot analysis. Furthermore, the apoptosis, proliferation, and viability of cells were evaluated by means of flow cytometry, 3\u2010(4,5\u2010dimethylthiazol\u20102\u2010yl)\u20102,5\u2010diphenyltetrazolium bromide (MTT) and colony formation assays. The results of microarray indicated miR\u2010145 as a differentially expressed biomarker between hypospadias tissues and normal tissues (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Moreover, rat models of hypospadias were observed with markedly lower vitamins A and E levels, reduced expressions of proteins relevant to oxidative stress (i.e., Nrf2, HO\u20101, Gpx, and SOD\u20101), as well as enhanced Bax and cleaved caspase\u20103 expressions (\n<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Furthermore, SOX9 was found to be targeted by miR\u2010145, and it was also modified by phosphorylated extracellular\u2010regulated kinase (p\u2010ERK), a portion of MAPK signaling (\n<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). The p\u2010ERK was significantly regulated after altering the expression of miR\u2010145 (\n<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Moreover, activation of p\u2010ERK and transfection of pcDNA\u2010SOX9 could cause higher expression of apoptins and larger apoptotic proportion of cells (\n<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), yet transfection of miR\u2010145 mimic led to improved cell apoptosis and depressed cell viability (\n<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). In conclusion, SOX9, which was regulated by both miR\u2010145 and miR\u2010145\/MAPK signaling, could be involved in the pathogenesis of hypospadias.<\/jats:p>","DOI":"10.1002\/jcp.27708","type":"journal-article","created":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T15:15:58Z","timestamp":1545232558000},"page":"10397-10410","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["MiR\u2010145\u2010modulated SOX9\u2010mediated hypospadias through acting on mitogen\u2010activated protein kinase signaling pathway"],"prefix":"10.1002","volume":"234","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8238-8787","authenticated-orcid":false,"given":"Yafeng","family":"Shang","sequence":"first","affiliation":[{"name":"Department of Urology Luoyang Central Hospital Affiliated to Zhengzhou University Luoyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanjie","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Urology Luoyang Central Hospital Affiliated to Zhengzhou University Luoyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiantao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Urology Luoyang Central Hospital Affiliated to Zhengzhou University Luoyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengtao","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Urology Luoyang Central Hospital Affiliated to Zhengzhou University Luoyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinhui","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Urology Luoyang Central Hospital Affiliated to Zhengzhou University Luoyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology Luoyang Central Hospital Affiliated to Zhengzhou University Luoyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,11,22]]},"reference":[{"key":"e_1_2_6_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2014.05.006"},{"key":"e_1_2_6_1_3_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.107086"},{"key":"e_1_2_6_1_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-3718"},{"key":"e_1_2_6_1_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2015.57"},{"issue":"1","key":"e_1_2_6_1_6_1","first-page":"30","article-title":"Current hypospadias techniques","volume":"2","author":"Ducket J. 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