| First Author | Balasubramanian S | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 9 | Pages | e45076 |
| PubMed ID | 22984613 | Mgi Jnum | J:191757 |
| Mgi Id | MGI:5462513 | Doi | 10.1371/journal.pone.0045076 |
| Citation | Balasubramanian S, et al. (2012) beta3 integrin in cardiac fibroblast is critical for extracellular matrix accumulation during pressure overload hypertrophy in mouse. PLoS One 7(9):e45076 |
| abstractText | The adhesion receptor beta3 integrin regulates diverse cellular functions in various tissues. As beta3 integrin has been implicated in extracellular matrix (ECM) remodeling, we sought to explore the role of beta3 integrin in cardiac fibrosis by using wild type (WT) and beta3 integrin null (beta3-/-) mice for in vivo pressure overload (PO) and in vitro primary cardiac fibroblast phenotypic studies. Compared to WT mice, beta3-/- mice upon pressure overload hypertrophy for 4 wk by transverse aortic constriction (TAC) showed a substantially reduced accumulation of interstitial fibronectin and collagen. Moreover, pressure overloaded LV from beta3-/- mice exhibited reduced levels of both fibroblast proliferation and fibroblast-specific protein-1 (FSP1) expression in early time points of PO. To test if the observed impairment of ECM accumulation in beta3-/- mice was due to compromised cardiac fibroblast function, we analyzed primary cardiac fibroblasts from WT and beta3-/- mice for adhesion to ECM proteins, cell spreading, proliferation, and migration in response to platelet derived growth factor-BB (PDGF, a growth factor known to promote fibrosis) stimulation. Our results showed that beta3-/- cardiac fibroblasts exhibited a significant reduction in cell-matrix adhesion, cell spreading, proliferation and migration. In addition, the activation of PDGF receptor associated tyrosine kinase and non-receptor tyrosine kinase Pyk2, upon PDGF stimulation were impaired in beta3-/- cells. Adenoviral expression of a dominant negative form of Pyk2 (Y402F) resulted in reduced accumulation of fibronectin. These results indicate that beta3 integrin-mediated Pyk2 signaling in cardiac fibroblasts plays a critical role in PO-induced cardiac fibrosis. |
