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Abstract: TH-PO431

Piperazine Ferulate Protects Mice Against Unilateral Ureteral Obstruction-Induced Interstitial Renal Fibrosis Through TGF-β/Smad3 Signaling

Session Information

Category: Glomerular Diseases

  • 1301 Glomerular Diseases: Fibrosis and Extracellular Matrix

Authors

  • Luo, Jun Hao, Sichuan Academy of Medical Sciences and Sichuan People's Hospital, Chengdu, Sichuan, China
  • Tang, Yun, Sichuan Academy of Medical Sciences and Sichuan People's Hospital, Chengdu, Sichuan, China
  • Li, Bo, Chengdu Hanpharm Limited Company, Cheng du, Sichuan, China
  • Xiao, Qiong, Sichuan Academy of Medical Sciences and Sichuan People's Hospital, Chengdu, Sichuan, China
  • Ding, Lu Han, Sichuan Academy of Medical Sciences and Sichuan People's Hospital, Chengdu, Sichuan, China
  • Zhong, Xiang, Sichuan Academy of Medical Sciences and Sichuan People's Hospital, Chengdu, Sichuan, China
  • Li, Yi, Sichuan Academy of Medical Sciences and Sichuan People's Hospital, Chengdu, Sichuan, China
  • Li, Guisen, Sichuan Academy of Medical Sciences and Sichuan People's Hospital, Chengdu, Sichuan, China
Background

Tubulointerstitial fibrosis is the ultimate pathological feature of CKD progression. Unfortunately, there is no clinical treatment with efficiency and no side effects. Piperazine ferulate (PF), a ferulic acid derivative, is commonly used as an adjunctive therapy for various types of glomerular diseases. However, the role of PF in tubulointerstitial fibrosis in CKD is still unclear. Current study aimed to elucidate the role and mechanism of PF in murine tubulointerstitial fibrosis with unilateral ureteral obstruction.

Methods

36 male C57 mice aged from 6 to 8 weeks were randomly divided into six groups (n=6): sham-operated group, interstitial fibrosis group, PF low dose intervention for interstitial fibrosis group, PF medium dose intervention for interstitial fibrosis group, PF high dose intervention for interstitial fibrosis group, PF alone group. Mice with unilateral ureteral obstruction were operated to establish a mouse model of interstitial fibrosis. And the mice accepted PF once per day by gavage following surgery. The mechanism of action of ferulic acid piperazine on interstitial fibrosis in mice was investigated by immunohistochemistry and western blotting.

Results

The results showed that the degree of fibrosis in the interstitial fibrosis group was severe, compared to that of mice in the sham-operated group. However, the degree of fibrosis in PF intervention following unilateral ureteral obstruction group was moderate. There was a significant positive correlation between this reduction and the dose of PF. Immunohistochemistry and western blotting showed that the protein expression levels of FN,Col-1,α-SMA,TGF-β1 and p-smad3 were significantly increased in the kidney tissues of mice with interstitial fibrosis. However, the protein expression levels of FN,Col-1,α-SMA,TGF-β1 and p-smad3 were significantly decreased in the kidney tissues of mice with interstitial fibrosis compared with those with ferulic acid piperazine intervention. And the expression of these proteins was significantly and negatively correlated with the dose of ferulic acid piperazine.

Conclusion

It indicated the protective role of PF in mice against unilateral ureteral obstruction-induced interstitial renal fibrosis through TGF-β/Smad3 signaling.