Journal article

Combined Blockade of Smad3 and JNK Pathways Ameliorates Progressive Fibrosis in Folic Acid Nephropathy

Mengjie Jiang, Jinjin Fan, Xinli Qu, Songhui Li, Susan K Niisson, Yu Bo Yang Sun, Yaping Chen, Di Yu, Dan Liu, Bi-Cheng Liu, Mingliang Tang, Wei Chen, Yi Pen, David J Nikolic-Paterson, Xiaoyun Jiang, Jinhua Li, Xueqing Yu

FRONTIERS IN PHARMACOLOGY | FRONTIERS MEDIA SA | Published : 2019

Abstract

Acute kidney injury leading to chronic kidney disease through tubulointerstitial fibrosis is a major challenge in nephropathy. Several signaling pathways promote interstitial fibrosis; however, effective suppression of fibrosis may require blockade of more than one pathway. This study investigated whether blockade of Smad3 and c-Jun N-terminal kinase (JNK) signaling gives added suppression of interstitial fibrosis in folic acid nephropathy. A single high dose of folic acid (FA) causes acute tubular damage in C57BL/6J mice followed by interstitial fibrosis and chronic renal impairment. Co-activations of Smad3 and JNK signaling occur in both tubular epithelial cells and myofibroblasts in areas..

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University of Melbourne Researchers

Grants

Awarded by National Natural Scientific Foundation of China (NSFC)


Awarded by Guangdong Medical University of Provincial and Municipal Construction of Colleges and Universities Project


Awarded by National Health and Medical Research Council (NHMRC) of Australia


Funding Acknowledgements

This study was supported by the National Natural Scientific Foundation of China (NSFC No. 81670667 to JL, 81670648 to XJ, 81800605 to MJ and 81600513 to DL), Guangdong Medical University of Provincial and Municipal Construction of Colleges and Universities Project (NO. 4SG18001Ga to JL) and the National Health and Medical Research Council (NHMRC) of Australia (APP1057581 to JL). MJ was supported by the International Program for Ph.D. Candidates, Sun Yat-sen University. DN-P has previously received funding from Celgene for studies of JNK inhibitors. The funder played no part in this study.