It is well established that Smad3 is a key downstream effector of transforming growth factor-β (TGF-β) signaling in tissue fibrogenesis. We reported here that targetting Smad3 specifically with a Smad3 inhibitor SIS3 is able to prevent or halt the progression of renal fibrosis in a mouse model of unilateral ureteral obstructive nephropathy (UUO). We found that preventive treatment with SIS3 at the time of disease induction largely suppressed progressive renal fibrosis by inhibiting α-smooth muscle actin (α-SMA) + myofibroblast accumulation and extracellular matrix (collagen I (Col.I) and fibronectin (FN)) production. Importantly, we also found that treatment with SIS3 on established mouse model of UUO from day 4 after UUO nephropathy halted the progression of renal fibrosis. Mechanistically, the preventive and therapeutic effects of SIS3 on renal fibrosis were associated with the inactivation of Smad3 signaling and inhibition of TGF-β1 expression in the UUO kidney. In conclusion, results from the present study suggest that targetting Smad3 may be a specific and effective therapy for renal fibrosis.
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July 2018
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The 3D structure of recombinant human deoxyribonuclease I. The N-terminal leucine shown in yellow at the top of the structure was selected for PEGylation of the protein. The amino acids shown in yellow towards the bottom of the protein are those interacting with globular actin, a potent inhibitor of human deoxyribonuclease I; for details, see pages 1439–1452.
Research Article|
July 09 2018
The preventive and therapeutic implication for renal fibrosis by targetting TGF-β/Smad3 signaling
Yun Zhang;
Yun Zhang
*
1Department of Dermatology, Foshan Hospital of Traditional Chinese Medicine, Foshan, China
2Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
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Xiao-Ming Meng;
Xiao-Ming Meng
*
2Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
4School of Pharmacy, Anhui Medical University, Anhui, China
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Xiao-Ru Huang;
Xiao-Ru Huang
2Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
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Hui Yao Lan
2Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
3Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong, Hong Kong, China
Correspondence: Hui Yao Lan (hylan@cuhk.edu.hk)
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Publisher: Portland Press Ltd
Received:
March 20 2018
Revision Received:
June 04 2018
Accepted:
June 05 2018
Accepted Manuscript online:
June 06 2018
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Clin Sci (Lond) (2018) 132 (13): 1403–1415.
Article history
Received:
March 20 2018
Revision Received:
June 04 2018
Accepted:
June 05 2018
Accepted Manuscript online:
June 06 2018
Citation
Yun Zhang, Xiao-Ming Meng, Xiao-Ru Huang, Hui Yao Lan; The preventive and therapeutic implication for renal fibrosis by targetting TGF-β/Smad3 signaling. Clin Sci (Lond) 18 July 2018; 132 (13): 1403–1415. doi: https://doi.org/10.1042/CS20180243
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