C3a and suPAR drive versican V1 expression in tubular cells of focal segmental glomerulosclerosis.

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 interac

SUBMITTER: Han R 

PROVIDER: S-EPMC6483651 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature