Collectivization of Vascular Smooth Muscle Cells via TGF-β-Cadherin-11-Dependent Adhesive Switching

Arteriosclerosis, Thrombosis, and Vascular Biology
Brittany BalintJ G Pickering

Abstract

Smooth muscle cells (SMCs) in healthy arteries are arranged as a collective. However, in diseased arteries, SMCs commonly exist as individual cells, unconnected to each other. The purpose of this study was to elucidate the events that enable individualized SMCs to enter into a stable and interacting cell collective. Human SMCs stimulated to undergo programmed collectivization were tracked by time-lapse microscopy. We uncovered a switch in the behavior of contacting SMCs from semiautonomous motility to cell-cell adherence. Central to the cell-adherent phenotype was the formation of uniquely elongated adherens junctions, up to 60 μm in length, which appeared to strap adjacent SMCs to each other. Remarkably, these junctions contained both N-cadherin and cadherin-11. Ground-state depletion super-resolution microscopy revealed that these hybrid assemblies were comprised of 2 parallel nanotracks of each cadherin, separated by 50 nm. Blocking either N-cadherin or cadherin-11 inhibited collectivization. Cell-cell adhesion and adherens junction elongation were associated with reduced transforming growth factor-β signaling, and exogenous transforming growth factor-β1 suppressed junction elongation via the noncanonical p38 pathway. Imagin...Continue Reading

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Citations

Sep 23, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Mark W Majesky
Dec 16, 2018·Cellular and Molecular Life Sciences : CMLS·Natalia Colás-Algora, Jaime Millán
Jan 15, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Brittany BalintHans-Joachim Schäfers
Feb 8, 2018·Cellular Signalling·Agne FrismantieneTherese J Resink
Apr 9, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Brittany BalintJean-Louis Guéant
Sep 11, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Camryn L JohnsonW David Merryman

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