[Folic acid supplementation alleviates high-salt diet-induced renal fibrosis in mice].

OBJECTIVES

To investigate the protective effect of 2-week dietary folic acid (FA) supplementation against renal fibrosis induced by high-salt (HS) diet in mice.

METHODS

Twenty-eight mice were randomly divided into control, HS (8% NaCl) diet group, HS+low-dose FA (FA: 0.56 mg/kg) group and HS+high-dose FA (5.6 mg/kg) group. The changes in body weight, food intake, water consumption, tail artery systolic pressure, and heart rate of the mice were monitored, and serum levels of creatinine (SCr) and inflammatory cytokines (IL-1β, IL-6, and TNF-α) were measured. Renal histopathology of the mice was assessed using HE, periodic acid-Schiff (PAS), Masson, and Sirius red staining. Renal expressions of Kim1, vimentin, α-Sma, and E-cadherin mRNAs and E-cadherin, vimentin, and α‑SMA proteins were detected using RT-qPCR and immunohistochemistry.

RESULTS

In mice feeding a HS diet, FA supplementation significantly reduced their water intake, lowered tail artery systolic pressure, heart rate, renal index and serum SCr levels, reducing also serum levels of TNF‑α , IL-1β, and IL-6. Masson and Sirius red staining revealed markedly reduced glomerular and interstitial fibrosis indices in HS+low-dose FA group, while the mice in HS+high-dose FA group showed mixed fibrotic improvements. Immunohistochemical results demonstrated that FA significantly upregulated E-cadherin protein expression and suppressed vimentin expression in renal tissues. Both FA doses inhibited HS-induced mRNA and protein expressions of fibrosis markers (Vimentin, Kim1 and α-Sma), attenuated interstitial collagen deposition, and alleviated renal fibrosis. FA also upregulated renal E-cadherin mRNA expression, contributing to fibrosis mitigation.

CONCLUSIONS

FA intervention ameliorates renal inflammation and delays fibrosis progression in HS-fed mice. Low-dose FA supplementation produces better protective effect than high-dose FA, likely mediated by regulation of renal E-cadherin, Kim1, vimentin, and α-Sma expressions.