Resveratrol Attenuates Adriamycin-Induced Focal Segmental Glomerulosclerosis through C3aR/C5aR- Sphingosine Kinase 1 Pathway

Abstract

Background/Aim: Focal segmental glomerulosclerosis (FSGS) typically presents with nephrotic range proteinuria, which could eventually develop into end-stage renal disease. Resveratrol (RSV) is a natural polyphenol compound, which has been reported to suppress inflammatory response and renal interstitial fibrosis. This study is aimed at evaluating the renoprotective effect of RSV treatment on adriamycin-induced FSGS. Methods: In Balb/c mice, adriamycin nephropathy was induced by adriamycin (10 mg/kg body weight, diluted in normal saline) via a tail vein on day 0. Then the mice were treated with RSV (40 mg/kg body weight) once daily by oral gavage, again starting on the day of adriamycin injection and continued for 6 weeks. At 6 weeks, the mice were sacrificed; kidneys and blood samples were collected for further analysis. Results: When treated with adriamycin, the expressions of C3aR, C5aR, sphingosine kinase 1 (Sphk1), and soluble urokinase-type plasminogen activator receptor (suPAR) were upregulated, while RSV treatment could inhibit the expressions of C3aR, C5aR, Sphk1, and suPAR, eventually leading to anti-inflammatory and anti-fibrosis conditions. Conclusion: RSV attenuates adriamycin-induced FSGS through C3aR/C5aR-Sphk1 pathway.

The Complement C3a and C3a Receptor Pathway in Kidney Diseases

“…In coronary artery disease, the expression of C3aR was positively correlated with activated glycoprotein IIb/IIIa in platelets, and the incidence of stroke and myocardial infarction was reduced in C3aR −/− mice (32). C3a/C3aR played a protective role in intestinal ischemia-reperfusion (IR) injury by inhibiting neutrophil mobilization (33).…”

“…In adriamycin (ADR)-treated mice, Liu et al found that C3aR expression was increased in the kidneys. Furthermore, it has been found that resveratrol suppressed inflammatory response, glomerulosclerosis, and renal interstitial fibrosis through down-regulation of the C3aR/C5aR-Sphk1 pathway (33).…”

Identification of biomarkers and pathways for focal segmental glomerulosclerosis using next generation sequencing data and bioinformatics analysis

“…Genes include APOL1 [9], INF2 [10], COL4A [11], MYO1E [12] and COL4A3 [13] are involved in the occurrence and development of FSGS. Signaling pathways include TGF-beta/Smad signaling pathway [14], JAK-STAT signaling pathway [15], Nrf2 signaling pathway [16], notch signaling pathway [17] and C3aR/C5aR-sphingosine kinase 1 pathway [18] plays a critical role in the pathophysiology of FSGS. Despite the increasing insights into several aspects of these mechanisms, a comprehensive overview of the integrated biological landscape underlying FSGS.…”

Inflammatory kidney injury in trichloroethylene hypersensitivity syndrome mice: Possible role of C3a receptor in the accumulation of Th17 phenotype

“…C3aR is expressed on cell membranes in many cell types, such as epithelial cells, macrophages, T lymphocytes and dendritic cells (Reichhardt and Meri, 2018). Recent studies show that C3aR signaling is involved in various renal inflammatory dysfunctions, including diabetic kidney disease (Li et al, 2015), atypical hemolytic uremic syndrome (Sartain et al, 2018), focal segmental glomerulosclerosis (Liu et al, 2017) and immunoglobulin A nephropathy (Zhang et al, 2017).…”