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Role of TGFβ1 and αvβ3‐integrin in the control of collagen type 1 turnover in response to angiotensin II and high glucose
Author(s) -
Palen Desiree I,
Matrougui Khalid
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a521-a
Subject(s) - medicine , endocrinology , angiotensin ii , chemistry , integrin , phosphorylation , transforming growth factor , kinase , type i collagen , biology , receptor , biochemistry
Hypertension and hyperglycemia are associated with resistance artery fibrosis leading to vasculopathy. We investigated the role of αvβ3‐integrin and TGFβ1 pathway on collagen type 1 up‐regulation, key element of structural remodeling, in mouse smooth muscle cells isolated from mesenteric resistance arteries, in response to high glucose (HG, 22 mM) or angiotensin II (AII, 100 nM). Methods and Results: VSMC were stimulated for 5 min or 48hrs with HG or AII and similarly increased cell lysate ERK1/2 MAP‐kinase phosphorylation and conditioned media latent TGFβ1 (100% control vs. 197±42; 196±9% respectively), αvβ3‐integrin (100% control vs. 151±5; 192±12% respectively), and collagen type 1 (100% control vs. 114±6; 161±42% respectively) assessed by immunoprecipitation and western blot analysis. Furthermore, TGFβ1 bioactivity assay (100% control vs. 172±5; 166±6%) and Smad2 phosphorylation (marker of TGFβ1 activation; 100% control vs. 149±8; 167±14%) were significantly increased in response to HG and AII. Immunostaining showed a network of collagen type 1 in response to HG and AII compared to control. The pretreatment of VSMC with ERK1/2 MAP‐Kinase (U0126, 1 μM), β3‐integrin antibody (1:100 dilution), specific αvβ3‐integrin inhibitor (SB223245, 10 μM) or siRNA‐TGFβ1 (100 nM) significantly prevented the increased collagen type 1 in response to AII and HG. Conclusion: This study provides evidence of a common pathway (ERK1/2, TGFβ1 and αvβ3‐integrin) involved in the regulation of collagen type 1 turnover in response to HG and AII and should be a potential target for overcoming vascular complications seen in diabetes and hypertension.