Transforming growth factor β1 suppresses proinflammatory gene program independent of its regulation on vascular smooth muscle differentiation and autophagy.

Cellular Signalling
Ping GaoXiaochun Long

Abstract

Transforming growth factor β (TGFβ) signaling plays crucial roles in maintaining vascular integrity and homeostasis, and is established as a strong activator of vascular smooth muscle cell (VSMC) differentiation. Chronic inflammation is a hallmark of various vascular diseases. Although TGFβ signaling has been suggested to be protective against inflammatory aortic aneurysm progression, its exact effects on VSMC inflammatory process and the underlying mechanisms are not fully unraveled. Here we revealed that TGFβ1 suppressed the expression of a broad array of proinflammatory genes while potently induced the expression of contractile genes in cultured primary human coronary artery SMCs (HCASMCs). The regulation of TGFβ1 on VSMC contractile and proinflammatory gene programs appeared to occur in parallel and both processes were through a SMAD4-dependent canonical pathway. We also showed evidence that the suppression of TGFβ1 on VSMC proinflammatory genes was mediated, at least partially through the blockade of signal transducer and activator of transcription 3 (STAT3) and NF-κB pathways. Interestingly, our RNA-seq data also revealed that TGFβ1 suppressed gene expression of a battery of autophagy mediators, which was validated by wes...Continue Reading

Citations

Feb 21, 2019·Experimental and Therapeutic Medicine·Qin ZhangJun Yang
May 31, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Ploingarm PetsophonsakulLeon Schurgers
Nov 17, 2020·Journal of the American Heart Association·Laura E BruijnJan H N Lindeman

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