{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T21:21:17Z","timestamp":1768252877170,"version":"3.49.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T00:00:00Z","timestamp":1615161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Promotion of Research at Tokyo University of Science","award":["25460255"],"award-info":[{"award-number":["25460255"]}]},{"name":"Promotion of Research at Tokyo University of Science","award":["JP19K16177"],"award-info":[{"award-number":["JP19K16177"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Oviduct, uterus, and vagina are derived from M\u00fcllerian ducts. But only in the vagina, the epithelium differentiates into stratified layers. Organ-specific secreted factors derived from the stroma of a neonatal mouse induce epithelial differentiation in the female reproductive tracts. However, the effects of the components and mechanical property of extracellular matrix (ECM) on the regulation of gene expression in the mesenchymal cells of neonatal stroma and differentiation of epithelium in the female reproductive tracts have been overlooked. In the present study, we have developed a simple 3D neonatal vaginal model using clonal cell lines to study the effect of ECM\u2019s components and stiffness on the epithelial stratification. Transcriptome analysis was performed by DNA-microarray to identify the components of ECM involved in the differentiation of vaginal epithelial stratification. The knockdown experiment of the candidate genes relating to vaginal epithelial stratification was focused on fibromodulin (Fmod), a collagen cross-linking protein. FMOD was essential for the expression of Bmp4, which encodes secreted factors to induce the epithelial stratification of vaginal mesenchymal cells. Furthermore, stiffer ECM as a scaffold for epithelial cells is necessary for vaginal epithelial stratification. Therefore, the components and stiffness of ECM are both crucial for the epithelial stratification in the neonatal vagina.<\/jats:p>","DOI":"10.1093\/biolre\/ioab041","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T07:18:28Z","timestamp":1615447108000},"page":"1239-1248","source":"Crossref","is-referenced-by-count":5,"title":["Extracellular matrix components and elasticity regulate mouse vaginal epithelial differentiation induced by mesenchymal cells"],"prefix":"10.1093","volume":"104","author":[{"given":"Tadaaki","family":"Nakajima","sequence":"first","affiliation":[{"name":"Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo, Japan"},{"name":"Institute of Industrial Science, The University of Tokyo, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miyabi","family":"Kozuma","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoko","family":"Hirasawa","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukiko T","family":"Matsunaga","sequence":"additional","affiliation":[{"name":"Institute of Industrial Science, The University of Tokyo, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Tomooka","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,3,8]]},"reference":[{"key":"2021060706380076800_ref1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0074-7696(08)60088-1","article-title":"Epithelial-stromal interactions in development of the urogenital tract","volume":"47","author":"Cunha","year":"1976","journal-title":"Int Rev Cytol"},{"key":"2021060706380076800_ref2","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1006\/dbio.2001.0458","article-title":"Epithelial-stromal tissue interaction in paramesonephric (M\u00fcllerian) epithelial differentiation","volume":"240","author":"Kurita","year":"2001","journal-title":"Dev Biol"},{"key":"2021060706380076800_ref3","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s00441-011-1161-2","article-title":"Involvement of activin signaling in abnormalities of mouse vagina exposed neonatally to diethylstilbestrol","volume":"344","author":"Nakajima","year":"2011","journal-title":"Cell Tissue Res"},{"key":"2021060706380076800_ref4","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.diff.2011.03.005","article-title":"The role of fibroblast growth factors on the differentiation of vaginal epithelium of neonatal mice","volume":"82","author":"Nakajima","year":"2011","journal-title":"Differentiation"},{"key":"2021060706380076800_ref5","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.ydbio.2013.06.024","article-title":"Diethylstilbestrol induces vaginal adenosis by disrupting SMAD\/RUNX1-mediated cell fate decision in the M\u00fcllerian duct epithelium","volume":"381","author":"Laronda","year":"2013","journal-title":"Dev Biol"},{"key":"2021060706380076800_ref6","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1210\/me.2016-1027","article-title":"Fgfr2iiib-mapk activity is required for epithelial cell fate decision in the lower m\u00fcllerian duct","volume":"30","author":"Terakawa","year":"2016","journal-title":"Mol Endocrinol"},{"key":"2021060706380076800_ref7","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.cell.2006.06.044","article-title":"Matrix elasticity directs stem cell lineage specification","volume":"126","author":"Engler","year":"2006","journal-title":"Cell"},{"key":"2021060706380076800_ref8","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1007\/s00441-015-2190-z","article-title":"Union is strength: Matrix elasticity and microenvironmental factors codetermine stem cell differentiation fate","volume":"361","author":"Lv","year":"2015","journal-title":"Cell Tissue Res"},{"key":"2021060706380076800_ref9","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1089\/ten.tea.2008.0473","article-title":"Engineered human skin fabricated using electrospun collagen-PCL blends: Morphogenesis and mechanical properties","volume":"15","author":"Powell","year":"2009","journal-title":"Tissue Eng - 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