{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T12:47:00Z","timestamp":1782823620765,"version":"3.54.5"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T00:00:00Z","timestamp":1781395200000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Preeclampsia (PE) is a major cause of maternal and fetal morbidity and mortality during pregnancy. PE is characterized by widespread endothelial dysfunction in mothers and fetuses. The etiology of PE remains elusive, but the dysregulation of microRNAs (miRNAs) in endothelial cells may contribute to the pathogenesis of PE. We have reported that PE downregulates expression of two miRNAs, miR\u201029a\u20103p and miR\u201029c\u20103p (miR\u201029a\/c\u20103p), and knockdown of miR\u201029a\/c\u20103p impairs functions of human umbilical vein endothelial cells (HUVECs). Herein, we tested the hypothesis that knockdown of miR\u201029a\/c\u20103p sex\u2010specifically impairs cellular responses to vascular endothelial growth factor\u2010A (VEGFA) and fibroblast growth factor 2 (FGF2) via disrupting the transcriptome in HUVECs. MiR\u201029a\/c\u20103p were knocked down using miR\u201029c\u20103p inhibitors in male and female HUVECs. Chemotactic and proliferative responses to VEGFA and FGF2 were assessed. RNA\u2010seq was performed to identify miR\u201029a\/c\u20103p regulated genes and pathways. Knockdown analysis demonstrated that miR\u201029c\u20103p inhibitors decreased miR\u201029a\/c\u20103p levels by over 95% in male and female HUVECs. Functionally, miR\u201029c\u20103p inhibitors suppressed VEGFA\u2010, but not FGF2\u2010stimulated chemotaxis by 26% in male, but not female HUVECs. RNA\u2010seq revealed that miR\u201029a\/c\u20103p inhibitors dysregulated 47 and 118 genes in male and female HUVECs, respectively. Bioinformatics analyses showed that miR\u201029a\/c\u20103p\u2010regulated genes were differently associated with hypertension, heart, angiogenesis, and immunology in male and female HUVECs. These data demonstrate that knockdown of miR\u201029a\/c\u20103p sex\u2010specifically affects cellular responses to VEGFA and FGF2 in HUVECs, possibly via disrupting the transcriptome and relevant pathways. These miR\u201029a\/c\u20103p\u2010regulated genes might represent promising sex\u2010specific therapeutic targets for PE\u2010associated endothelial dysfunction pending further in vivo and clinical verification.<\/jats:p>","DOI":"10.1002\/jcp.70199","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T06:27:57Z","timestamp":1781504877000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sexually Dimorphic Regulation of MiR\u201029a\/c\u20103p in Human Endothelial Cells: Cell Functions and Transcriptome"],"prefix":"10.1002","volume":"241","author":[{"given":"Si\u2010yan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Wisconsin\u2013Madison Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colman I.","family":"Freel","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Wisconsin\u2013Madison Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Animal and Comparative Biomedical Sciences University of Arizona Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2224-2372","authenticated-orcid":false,"given":"Jing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Wisconsin\u2013Madison Madison Wisconsin 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