2008
DOI: 10.1002/art.23436
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Src kinases in systemic sclerosis: Central roles in fibroblast activation and in skin fibrosis

Abstract: Objective. Src kinases are nonreceptor tyrosine kinases, which have been implicated in cytoskeletal organization and cell mobility. This study was undertaken to evaluate the potential of Src kinases as novel targets of antifibrotic therapies.Methods. Fibroblast cultures were obtained from 10 patients with systemic sclerosis (SSc) and 5 healthy subjects. Src signaling was inhibited using smallmolecule inhibitors and overexpression of a dominantnegative mutant of Src and of the endogenous inhibitor Csk. The expr… Show more

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Cited by 113 publications
(87 citation statements)
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“…These profibrotic effects of TGF-b1 were inhibited by AZD0530 in human lung fibroblasts. Our results are consistent with previous findings that inhibition of Src kinase prevents collagen synthesis in cardiac and skin fibroblasts (Elkareh et al, 2007;Skhirtladze et al, 2008). a-SMA is critical for myofibroblast contractility (Hinz et al, 2007); therefore, reduced a-SMA expression leads to the reduced contractility in lung fibroblasts treated with AZD030.…”
Section: Discussionsupporting
confidence: 93%
“…These profibrotic effects of TGF-b1 were inhibited by AZD0530 in human lung fibroblasts. Our results are consistent with previous findings that inhibition of Src kinase prevents collagen synthesis in cardiac and skin fibroblasts (Elkareh et al, 2007;Skhirtladze et al, 2008). a-SMA is critical for myofibroblast contractility (Hinz et al, 2007); therefore, reduced a-SMA expression leads to the reduced contractility in lung fibroblasts treated with AZD030.…”
Section: Discussionsupporting
confidence: 93%
“…Fivemicrometer sections were stained with hematoxylin and eosin. Dermal thickness was analyzed at 100-fold magnification by measuring the distance between the epidermal-dermal junction and the dermal-subcutaneous fat junction at 3 sites in lesional skin in each mouse (13). Collagen fibers were visualized by Masson's trichrome staining, according to the recommendations of the manufacturer (Sigma-Aldrich, Munich, Germany), and analyzed at 1,000-fold magnification.…”
Section: Methodsmentioning
confidence: 99%
“…TH17 lymphocytes promote the expression of the pro-fibrotic cytokines in scleroderma [53]. In addition, pp60 src released from the AHR on ligand binding plays a role in fibroblast activation [54].…”
Section: The Relationship Between the Cytokine Profile And The Aryl Hmentioning
confidence: 99%