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Fyn deficiency attenuates renal fibrosis by inhibition of phospho-STAT3

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Author(s)
Hye-Young SeoJae-Han JeonYun-A JungGwon-Soo JungEun Ju LeeYoung-Keun ChoiKeun-Gyu ParkMi Sun ChoeByoung Kuk JangMi-Kyung KimIn-Kyu Lee
Keimyung Author(s)
Choe, Mi SunJang, Byoung KukKim, Mi Kyung
Department
Dept. of Pathology (병리학)
Dept. of Internal Medicine (내과학)
Journal Title
Kidney International
Issued Date
2016
Volume
90
Issue
6
Keyword
TGF-β
Abstract
The hallmark of renal tubulointerstitial fibrosis is the accumulation of myofibroblasts and extracellular matrix proteins. Fyn, a member of the Src family of kinases, has diverse biological functions including regulation of mitogenic signaling and proliferation and integrin-mediated interaction. Src family proteins promote pulmonary fibrosis by augmenting transforming growth factor-β signaling, but their role in renal fibrosis is less understood. We observed upregulation of Fyn in a renal fibrosis model induced by unilateral ureteral obstruction. Upon ureteral obstruction, Fyn-deficient mice exhibited attenuated renal fibrosis relative to wild-type mice. Furthermore, obstruction-induced renal expression of type I collagen, fibronectin, α-smooth muscle actin, and plasminogen activator inhibitor-1 was suppressed. Pharmacologic inhibition of Fyn blocked induction of extracellular matrix proteins in kidney cell lines. Importantly, the attenuation of renal fibrosis by Fyn deficiency was not accompanied by changes in the Smad pathway. Rather, the antifibrotic effect of Fyn deficiency was associated with downregulation of signal transducer and activator of transcription 3 (STAT3). Small, interfering RNA targeting STAT3 in Fyn-deficient cells further suppressed α-smooth muscle actin expression, whereas a STAT3 activator partially restored plasminogen activator inhibitor-1 expression, indicating that STAT3 signaling is critically involved in this process. Thus, Fyn plays an important role in renal fibrosis. Hence, Fyn kinase inhibitors may be therapeutically useful against renal fibrosis.
Keimyung Author(s)(Kor)
최미선
장병국
김미경
Publisher
School of Medicine
Citation
Hye-Young Seo et al. (2016). Fyn deficiency attenuates renal fibrosis by inhibition of phospho-STAT3. Kidney International, 90(6), 1285–1297. doi: 10.1016/j.kint.2016.06.038
Type
Article
ISSN
0085-2538
Source
https://linkinghub.elsevier.com/retrieve/pii/S0085253816303520
DOI
10.1016/j.kint.2016.06.038
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/32816
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
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