Abstract
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 TA-GLN 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | C502-C515 |
| Journal | American Journal of Physiology - Cell Physiology |
| Volume | 315 |
| Issue number | 4 |
| DOIs | |
| State | Published - Oct 1 2018 |
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Keywords
- Diabetes
- Endothelial
- Migration
- Progenitor
- Transgelin
- Vasculogenesis
ASJC Scopus subject areas
- Physiology
- Cell Biology
Cite this
Transgelin induces dysfunction of fetal endothelial colony-forming cells from gestational diabetic pregnancies. / Varberg, Kaela M.; Garretson, Rashell O.; Blue, Emily K.; Chu, Chenghao; Gohn, Cassandra R.; Tu, Wanzhu; Haneline, Laura.
In: American Journal of Physiology - Cell Physiology, Vol. 315, No. 4, 01.10.2018, p. C502-C515.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Transgelin induces dysfunction of fetal endothelial colony-forming cells from gestational diabetic pregnancies
AU - Varberg, Kaela M.
AU - Garretson, Rashell O.
AU - Blue, Emily K.
AU - Chu, Chenghao
AU - Gohn, Cassandra R.
AU - Tu, Wanzhu
AU - Haneline, Laura
PY - 2018/10/1
Y1 - 2018/10/1
N2 - 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 TA-GLN 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.
AB - 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 TA-GLN 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.
KW - Diabetes
KW - Endothelial
KW - Migration
KW - Progenitor
KW - Transgelin
KW - Vasculogenesis
UR - http://www.scopus.com/inward/record.url?scp=85055344924&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055344924&partnerID=8YFLogxK
U2 - 10.1152/ajpcell.00137.2018
DO - 10.1152/ajpcell.00137.2018
M3 - Article
C2 - 29949406
AN - SCOPUS:85055344924
VL - 315
SP - C502-C515
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6143
IS - 4
ER -