Transgelin induces dysfunction of fetal endothelial colony-forming cells from gestational diabetic pregnancies

التفاصيل البيبلوغرافية
العنوان: Transgelin induces dysfunction of fetal endothelial colony-forming cells from gestational diabetic pregnancies
المؤلفون: Emily K. Blue, Chenghao Chu, Cassandra R. Gohn, Wanzhu Tu, Kaela M. Varberg, Laura S. Haneline, Rashell O. Garretson
المصدر: American journal of physiology. Cell physiology. 315(4)
سنة النشر: 2018
مصطلحات موضوعية: 0301 basic medicine, Adult, medicine.medical_specialty, endocrine system diseases, Physiology, Transgelin, Muscle Proteins, Neovascularization, Physiologic, Disease, 030204 cardiovascular system & hematology, Fetal exposure, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Vasculogenesis, Fetus, Cell Movement, Pregnancy, Diabetes mellitus, Internal medicine, medicine, Humans, Cells, Cultured, business.industry, Stem Cells, Microfilament Proteins, Endothelial Cells, Cell Biology, medicine.disease, Gestational diabetes, Diabetes, Gestational, 030104 developmental biology, Endocrinology, Gestation, Female, business, Research Article
الوصف: Fetal exposure to gestational diabetes mellitus (GDM) predisposes children to future health complications including hypertension and cardiovascular disease. A key mechanism by which these complications occur is through the functional impairment of vascular progenitor cells, including endothelial colony-forming cells (ECFCs). Previously, we showed that fetal ECFCs exposed to GDM have decreased vasculogenic potential and altered gene expression. In this study, we evaluate whether transgelin (TAGLN), which is increased in GDM-exposed ECFCs, contributes to vasculogenic dysfunction. TAGLN is an actin-binding protein involved in the regulation of cytoskeletal rearrangement. We hypothesized that increased TAGLN expression in GDM-exposed fetal ECFCs decreases network formation by impairing cytoskeletal rearrangement resulting in reduced cell migration. To determine if TAGLN is required and/or sufficient to impair ECFC network formation, TAGLN was reduced and overexpressed in ECFCs from GDM and uncomplicated pregnancies, respectively. Decreasing TAGLN expression in GDM-exposed ECFCs improved network formation and stability as well as increased migration. In contrast, overexpressing TAGLN in ECFCs from uncomplicated pregnancies decreased network formation, network stability, migration, and alignment to laminar flow. Overall, these data suggest that increased TAGLN likely contributes to the vasculogenic dysfunction observed in GDM-exposed ECFCs, as it impairs ECFC migration, cell alignment, and network formation. Identifying the molecular mechanisms underlying fetal ECFC dysfunction following GDM exposure is key to ascertain mechanistically the basis for cardiovascular disease predisposition later in life.
تدمد: 1522-1563
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d44358cf1cc561caada9ed4e385e99b6
https://pubmed.ncbi.nlm.nih.gov/29949406
Rights: OPEN
رقم الانضمام: edsair.doi.dedup.....d44358cf1cc561caada9ed4e385e99b6
قاعدة البيانات: OpenAIRE