Complement C3 exacerbates renal interstitial fibrosis by facilitating the M1 macrophage phenotype in a mouse model of unilateral ureteral obstruction.

In this study, we investigated the contribution of C3 on macrophage polarization and renal fibrosis in C3 deficient unilateral ureteral obstruction (UUO) mice and bone marrow-derived macrophages (BMDMs). C3 deficient mice exhibited attenuated renal fibrosis and ameliorated peritubular capillary rarefaction. Lack of C3 contributed to M2 macrophage polarization, increased IL-10 and VEGF164, decreased TNF-α and sVEGFR1 expression in the obstructed kidneys at the early stages of UUO. C3a facilitated LPS-induced M1 polarization and inflammatory factor production in BMDM in vitro, accompanied by increased ERK, NF-κB, and STAT1 phosphorylation. The ERK specific inhibitor PD98059 inhibited the phosphorylation of ERK, NF-κB and STAT1, and attenuated M1 polarization related inflammatory factor production. Further, the culture supernatant from M1 macrophages and C3a-treated M2 macrophages were more detrimental to angiogenesis compared with M2 macrophage supernatants. Thus, complement C3 exacerbates renal interstitial fibrosis by facilitating macrophage M1 polarization, promoting proinflammatory cytokines expression, deteriorating peritubular capillary rarefaction in kidney. PMID: 31461345 [PubMed - as supplied by publisher]
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research