Fibulin-4 deficiency differentially affects cytoskeleton structure and dynamics as well as TGF beta signaling
2019
textabstractFibulin-4 is an extracellular matrix (ECM) protein essential for elastogenesis and mutations in this protein lead to
aneurysm formation. In this study, we isolated vascular smooth muscle cells (VSMCs) from mice with reduced
fibulin-4 protein expression (Fibulin-4R/R) and from mice with a smooth muscle cell specific deletion of the
Fibulin-4 gene (Fibulin-4f/−/SM22Cre+). We subsequently analyzed and compared the molecular consequences
of reduced Fibulin-4 expression versus total ablation of Fibulin-4 expression with regard to effects on the SMC
specific contractile machinery, cellular migration and TGFβ signaling.
Analysis of the cytoskeleton showed that while Fibulin-4f/−/SM22Cre+ VSMCs lack smooth muscle actin
(SMA) fibers, Fibulin-4R/R VSMCs were able to form SMA fibers. Furthermore, Fibulin-4f/−
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