Abstract: SA-PO603
The Role of Angiogenin/miR-141 Axis in Glomerular Injury of IgA Nephropathy
Session Information
- Glomerular Diseases: Immunology, Inflammation - II
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Author
- Weng, Chunhua, the First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
Background
IgA nephropathy (IgAN) is the most common primary chronic glomerular disease worldwide. Gal-deficient IgA1 (Gd-IgA1) containing immune complex is the important factor involved in the pathogenesis of IgAN, which mechanism has not yet been clarified. Angiogenin is a secreted ribonuclease, and it plays biological functions through selectively cutting RNA substrates, including miRNAs.
Methods
The concentration of Angiogenin in plasma and cell medium was examined by Elisa. Overexpression of Angiogenin was conducted by infection of lentivirus with Angiogenin overexpression plasmid. Knockdown of Angiogenin was conducted by infection of lentivirus with shRNA. Cell proliferation activity was carried out by CCK-8. Cell apoptosis was carried out by Flow cytometry. The protein were measured by western blotting, mRNA and miRNA were measured by RT-qPCR. The cleavage of miR-141 by Angiogenin was carried out by a cell-free cleavage assay.
Results
The level of Angiogenin in plasma was elevated in IgAN patients than healthy controls. When the glomerular mesangial cell was stimulated by Gd-IgA1 immune complex, the secretion of Angiogenin and some inflammatory cytokines were upregulated. When the expression of Angiogenin in mesangial cell was knock-down by shRNA, the proliferative activity of mesangial cells was inhibited. The expression level of miR-141 was affected by Angiogenin expression in mesangial cells, high expression of Angiogenin downregulated miR-141 and knockdown of Angiogenin upregulated the level of miR-141. In addition, Angiogenin digest miR-141 as an endoribonuclease in vitro.
Conclusion
Angiogenin was upregulated in IgAN . Gd-IgA1 complex stimulation increased the secretion of Angiogenin and inflammatory cytokines of mesangial cell. Down-regulation of Angiogenin inhibits the proliferative activity of mesangial cells. Angiogenin regulates the level of miR-141 in mesangial cell and digests miR-141 as an endoribonuclease in vitro. Thus, Angiognein/miR-141 axis may regulate IgAN through affecting mesangial cell proliferation and inflammatory cytokines secretion.
Funding
- Government Support - Non-U.S.