Hederagenin (HE) plays a protective role by inhibiting cell proliferation and ameliorating
fibrosis. The current
therapy for
Chronic kidney disease (CKD) often result in the risks of side effects. The present study aimed to explore whether it can protect against renal
fibrosis and unveil the underlying mechanism.
Transforming growth factor (TGF)-β was used to induce the fibroblasts NRK-49 F for the simulation of renal
fibrosis. The cell viability and expression of
fibrosis-related
proteins in TGF-β-treated NRK-49 F cells was, respectively, measured by Cell Counting Kit-8 (CCK-8) and western blot. After predicting the target genes of HE, M3 receptor was measured in NRK-49 F cells treated with TGF-β alone or in combination with HE. Then, M3 receptor was silenced in TGF-β-treated NRK-49 F cells for the detection of its role in proliferation and
fibrosis.
Muscarinic acetylcholine receptor M3 (M3 receptor) agonist
pilocarpine was further added to determine the role of M3 receptor involved. HE inhibited the proliferation and
fibrosis of TGF-β-treated NRK-49 F cells. M3 receptor was predicted to be a target of HE. Moreover, interference of M3 receptor improved the proliferation and
fibrosis of TGF-β-treated NRK-49 F cells. Further addition of
pilocarpine reversed the inhibitory effect of HE on proliferation and
fibrosis of TGF-β-treated NRK-49 F cells. HE protects against renal
fibrosis in NRK-49 F cells by targeting
Muscarinic acetylcholine receptor, which will provide theoretical basis for the clinical use of HE for kidney-related disease treatment.