Folic acid supplementation alleviates high-salt diet-induced renal fibrosis in mice
TANG Fang
WANG Yongyi
LIANG Tingting
HE Weiying
LAO Huilv
SONG Jiale
Abstract：Objective 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.Conclusion 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.
Keywords：short-term high saltrenal damagefolic acid interventionrenal fibrosis
Publication Date：2026-03-20
Online Publishing Date：2026-04-01(First online date of this platform, not the publication date of the document)
Pages：8( 707-714 )