Postnatal Smad3 Inactivation in Murine Smooth Muscle Cells Elicits a Temporally and Regionally Distinct Transcriptional Response.

ABSTRACT: Heterozygous, loss of function mutations in positive regulators of the Transforming Growth Factor-β (TGF-β) pathway cause hereditary forms of thoracic aortic aneurysm. It is unclear whether and how the initial signaling deficiency triggers secondary signaling upregulation in the remaining functional branches of the pathway, and if this contributes to maladaptive vascular remodeling. To examine this process in a mouse model in which time-controlled, partial interference with postnatal TGF-β signaling in vascular smooth muscle cells (VSMCs) could be assessed, we used a VSMC-specific tamoxifen-inducible system, and a conditional allele, to inactivate Smad3 at 6 weeks of age, after completion of perinatal aortic development. This intervention induced dilation and histological abnormalit

SUBMITTER: Bramel EE 

PROVIDER: S-EPMC9033237 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature