A role for spleen tyrosine kinase in renal fibrosis in the mouse obstructed kidney

Life Sciences
Frank Y MaD J Nikolic-Paterson

Abstract

Spleen tyrosine kinase (Syk) is a non-receptor tyrosine kinase involved in the signalling pathways of the B cell receptor, Fcγ-receptor and some leukocyte integrins. However, Syk can also be expressed by some non-haematopoietic cell types, although whether Syk signalling in these cells contributes to the pathogenesis of kidney disease is unknown. To address this question, we examined the function of Syk in antibody-independent renal interstitial fibrosis in the unilateral ureteric obstruction (UUO) model. Groups of C57BL/6J mice were treated with a selective Syk inhibitor (CC0417, 30 mg/kg/bid), vehicle, or no treatment, from the time of surgery until being killed 7 days later. A substantial accumulation of interstitial Syk(+) cells was seen in the UUO kidney. Double staining identified Syk expression by infiltrating macrophages and by a subset of α-SMA(+) myofibroblasts. CC0417 treatment substantially reduced the Syk(+) cell population in conjunction with a reduction in both myofibroblast and macrophage accumulation. This was associated with a substantial reduction in collagen IV deposition and mRNA levels of pro-fibrotic (collagen I, collagen IV, fibronectin, α-SMA, TGF-β1 and PAI-1) and pro-inflammatory molecules (MCP-1, TNF...Continue Reading

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Citations

Mar 15, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Chen QuJian Hong
Jun 21, 2018·International Journal of Immunopathology and Pharmacology·Yingjie HanDavid J Nikolic-Paterson
Jan 30, 2019·Nature Reviews. Nephrology·Patrick Ming-Kuen TangHui-Yao Lan
Aug 20, 2021·Cellular and Molecular Gastroenterology and Hepatology·Carmelo LuciPhilippe Gual

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