Kidney Week

Abstract: FR-PO371

Oleanolic Acid Alleviates Renal Fibrosis through Regulating the Expression of miR-141

Session Information

• Mechanisms Associated with Kidney Fibrosis - I
  November 03, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Chronic Kidney Disease (Non-Dialysis)

• 308 CKD: Mechanisms of Tubulointerstitial Fibrosis

Authors

• Wei, Minggang, The First Affiliated Hospital of Soochow University, Suzhou, China

Minggang Wei,

• Yin, Jiaqi, The First Affiliated Hospital of Soochow University, Suzhou, China

Jiaqi Yin,

Background

Renal fibrosis is characterized by the abnormal metabolism of extracellular matrix (ECM). However, ECM’s abnormal metabolism mechanism has not been understood clearly. Recent studies suggested that metabolic regulation of ECM may be associated with some miRNA, such as miR-141, miR-21, miR-136 and so on. MiR-141 is the most important of them which control the ECM’s metabolism. Both the cell signal pathway of TGF- β₁/Smads and the ECM’s metabolism enzyme MMP-9 play important roles in renal fibrosis through effecting ECM’s metabolism. So we hypothesize that miR-141 regulation the ECM’s metabolism via both TGF- β₁/Smads and MMP-9. Oleanolic acid (OA) is the main extract of Achyranthes bidentate, which could reduce the symptoms of chronic kidney disease and improve the renal function. We have proved that OA can decrease the degree of renal fibrosis through regulating the metabolism of ECM. Therefore, we speculated that OA could lessen the excessive accumulation of ECM by enhancing the expression of miR-141.

Methods

Thirty-two healthy Balb/c male mice performed unilateral ureteral obstruction (UUO) surgery to induce ECM accumulation. Mice were randomly divided into 4 groups: sham-operated group (n=8), UUO group (n=8), OA (25mL/kg) group (n=8), Lotensin (25mL/kg) group (n=8). Daily OA and Lotensin was applied to mice by oral gavage for 10 days after surgery. Then all mice were killed and renal tissue were obtained for further analysis.

Results

We showed that OA group revealed obviously pathological injury including renal interstitial fibrosis compared with the model group by HE staining. And the expression of TGF-β1, Smad2/3, ColIV, FN were downregulated and the expression of MMP-9 was upregulated compared with the model group by immunohistochemistry (P < 0.05). Real-time quantitative PCR demonstrated that OA group increased significantly the expression of miR-141 and MMP-9, while obviously decreased the expression of TGF-β1, Smad2/3, ColIV and FN, compared with the model group (P < 0.05).

Conclusion

In summary, our study provides that OA could regulate the expression of miR-141 to release the abnormal accumulation of ECM through impacting TGF- β₁/Smads. On the other hand, OA could increase the expression of miR-141 to inhibit the excessive accumulation of ECM via upregulating the expression of MMP-9. OA may have beneficial effects on inhibiting the development of renal fibrosis.

Funding

• Government Support - Non-U.S.