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Kidney Week

Abstract: FR-PO396

CircRNA_15698 Exacerbates Folic Acid-Induced Renal Interstitial Fibrosis via the miR-185/TGF-β1 Pathway

Session Information

  • CKD: Mechanisms - II
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Wang, Dongdong, China medical university, Shenyang, China
  • Luan, Junjun, The Affiliated Shengjing Hospital of China Medical School, Shenyang/China, LIAONING, China
  • Zhou, Hua, The Affiliated Shengjing Hospital of China Medical School, Shenyang/China, LIAONING, China
Background

Circular RNAs (circRNAs) are a novel type of noncoding RNAs that modulate the pathogenesis of multiple diseases. A study reports that circRNA_15698 aggravates the renal mesangial extracellular matrix of diabetic nephropathy via miR-185/TGF-β1. However, the role of circRNA_15698 in renal tubulointerstitial fibrosis remains unclear. In this study, we aim to investigate whether circRNA_15698 plays an important role in folic acids (FA)-induced renal interstitial fibrosis and its corresponding mechanism.

Methods

Male CD1mice were peritoneally injected 250 mg/kg of FA or its vehicle. We collected kidney tissue after removing blood by PBS perfusion on day 30 after FA injection and evaluated renal interstitial fibrosis by PAS and Masson staining. We measured mRNA levels of pro-inflammatory cytokines such as interleukin-6 (Il6), tumor necrosis factor-α (Tnfα), and inflammatory cells including T lymphocytes and macrophages in the kidneys. We also examined the expression of pro-fibrosis factors, alpha smooth muscle actin (a-SMA), Collagen I (COL-1), and Fibronectin. Finally, we examined the renal expression of circRNA_15698, miR-185, transforming growth factor-beta (Tgfb) and analyzed the math seeds between circRNA_15698 and miR-185 as well as between miR-185 and Tgfb on TargetScan and miRanda.

Results

Peritoneal injection of FA induced obvious renal interstitial fibrosis (RIF) seen on PAS and Masson staining on day 30 after the injection. Pro-inflammatory cytokines, both Il6 and Tnfα elevated remarkably in FA-injected mice compared to normal control mice. The infiltration of T lymphocytes and macrophages were seen in the kidneys. Pro-fibrosis factors, a-SMA, COL-1, and Fibronectin were increased in renal FA-injected mice on both mRNA and protein levels of the above factors. In addition, the renal expression of circRNA_15698 was upregulated, renal miR-185 was downregulated and Tfgb was also upregulated. Finally we found perfect match seed displayed between circRNA_15698 and miR-185 as well as between miR-185 and Tgfb on TargetScan and miRanda analysis.

Conclusion

Our results suggested that circRNA_15698 might play an important role in FA-induced renal interstitial fibrosis by sponging miR-185 and increasing production of profibrotic TGF-β1. This is a novel pathway in pathogenesis of renal fibrosis and circRNA_15698 might be a new therapeutic target for renal fibrosis.

Funding

  • Government Support - Non-U.S.