C3a and suPAR drive versican V1 expression in tubular cells of focal segmental glomerulosclerosis
Runhong Han, Shuai Hu, Weisong Qin, Jinsong Shi, Qin Hou, Xia Wang, Xiaodong Xu, Minchao Zhang, Caihong Zeng, Zhihong Liu, and Hao Bao
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First published July 11, 2019 - More info
JCI Insight. 2019;4(13):e130986. https://doi.org/10.1172/jci.insight.130986.
© 2019 American Society for Clinical Investigation
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Abstract
Chronic tubulointerstitial injury impacts the prognosis of focal segmental glomerulosclerosis (FSGS). We found that the level of versican V1 was increased in tubular cells of FSGS patients. Tubular cell–derived versican V1 induced proliferation and collagen synthesis by activating the CD44/Smad3 pathway in fibroblasts. Both urine C3a and suPAR were increased and bound to the tubular cells in FSGS patients. C3a promoted the transcription of versican by activating the AKT/β-catenin pathway. C3aR knockout decreased the expression of versican in Adriamycin-treated (ADR-treated) mice. On the other hand, suPAR bound to integrin β6 and activated Rac1, which bound to SRp40 at the 5′ end of exon 7 in versican pre-mRNA. This binding inhibited the 3′-end splicing of intron 6 and the base-pair interactions between intron 6 and intron 8, leading to the formation of versican V1. Cotreatment with ADR and suPAR specifically increased the level of versican V1 in tubulointerstitial tissues and caused more obvious interstitial fibrosis in mice than treatment with only ADR. Altogether, our results show that C3a and suPAR drive versican V1 expression in tubular cells by promoting transcription and splicing, respectively, and the increases in tubular cell–derived versican V1 induce interstitial fibrosis by activating fibroblasts in FSGS.
Authors
Runhong Han, Shuai Hu, Weisong Qin, Jinsong Shi, Qin Hou, Xia Wang, Xiaodong Xu, Minchao Zhang, Caihong Zeng, Zhihong Liu, Hao Bao
Original citation: JCI Insight. 2019;4(7):e122912. https://doi.org/10.1172/jci.insight.122912
Citation for this corrigendum: JCI Insight. 2019;4(13):e130986. https://doi.org/10.1172/jci.insight.130986
The affiliations were incorrect. The correct author list and affiliations are below.
Runhong Han,1,2 Shuai Hu,2 Weisong Qin,2 Jinsong Shi,2 Qin Hou,2 Xia Wang,2 Xiaodong Xu,2 Minchao Zhang,2 Caihong Zeng,2 Zhihong Liu,1,2 and Hao Bao1,2
1Southeast University School of Medicine, National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing, China. 2National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
The authors regret the errors.
