Pericellular fibronectin is required for RhoA-dependent responses to cyclic strain in fibroblasts

Lutz, Roman; Sakai, Takao; Chiquet, Matthias (2010). Pericellular fibronectin is required for RhoA-dependent responses to cyclic strain in fibroblasts. Journal of cell science, 123(Pt 9), pp. 1511-21. Cambridge: Company of Biologists Limited 10.1242/jcs.060905

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To test the hypothesis that the pericellular fibronectin matrix is involved in mechanotransduction, we compared the response of normal and fibronectin-deficient mouse fibroblasts to cyclic substrate strain. Normal fibroblasts seeded on vitronectin in fibronectin-depleted medium deposited their own fibronectin matrix. In cultures exposed to cyclic strain, RhoA was activated, actin-stress fibers became more prominent, MAL/MKL1 shuttled to the nucleus, and mRNA encoding tenascin-C was induced. By contrast, these RhoA-dependent responses to cyclic strain were suppressed in fibronectin knockdown or knockout fibroblasts grown under identical conditions. On vitronectin substrate, fibronectin-deficient cells lacked fibrillar adhesions containing alpha5 integrin. However, when fibronectin-deficient fibroblasts were plated on exogenous fibronectin, their defects in adhesions and mechanotransduction were restored. Studies with fragments indicated that both the RGD-synergy site and the adjacent heparin-binding region of fibronectin were required for full activity in mechanotransduction, but not its ability to self-assemble. In contrast to RhoA-mediated responses, activation of Erk1/2 and PKB/Akt by cyclic strain was not affected in fibronectin-deficient cells. Our results indicate that pericellular fibronectin secreted by normal fibroblasts is a necessary component of the strain-sensing machinery. Supporting this hypothesis, induction of cellular tenascin-C by cyclic strain was suppressed by addition of exogenous tenascin-C, which interferes with fibronectin-mediated cell spreading.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > School of Dental Medicine > Department of Orthodontics
UniBE Contributor:	Chiquet, Matthias
ISSN:	0021-9533
Publisher:	Company of Biologists Limited
Language:	English
Submitter:	Eveline Carmen Schuler
Date Deposited:	04 Oct 2013 14:08
Last Modified:	05 Dec 2022 14:00
Publisher DOI:	10.1242/jcs.060905
PubMed ID:	20375066
Web of Science ID:	000276912300015
URI:	https://boris.unibe.ch/id/eprint/455 (FactScience: 199345)