Abstract: TH-PO504
Critical Role of lincRNA-p21 in Mediating Lipotoxicity-Induced Kidney Injury
Session Information
- CKD: Mechanisms - I
November 07, 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
- Li, Bin, The University of Hong Kong, Hong Kong, China
- Leung, Joseph C K, The University of Hong Kong, Hong Kong, China
- Chan, Loretta Y.Y., Queen Mary Hospital, Hong Kong, HONG KONG, China
- Yiu, Wai Han, The University of Hong Kong, Hong Kong, China
- Lai, Kar Neng, The University of Hong Kong, Hong Kong, China
- Tang, Sydney C.W., The University of Hong Kong, Hong Kong, China
Background
Ectopic lipid accumulation in kidney is a key factor in the etiology of lipotoxicity-induced kidney lesion. Emerging evidence unravels that long intergenic non-coding RNA p21 (lincRNA-p21) plays a pivotal role in diverse biological processes and diseases. However, little is known about the role of lincRNA-p21 in kidney diseases. We aim to identify the functional role of lincRNA-p21 in lipotoxicity-induced kidney injury.
Methods
Expression of lincRNA-p21 in kidney from mice (C57BL/6J) fed with normal diet (ND; 10 kcal%) or high-fat diet (HFD; 60 kcal%), as well as in palmitic acid (PA)-treated human proximal tubular epithelial cells line (HK-2 cells) was determined by qRT-PCR. Antisense locked nucleic acids (LNA) GapmeR technique was utilized to silence lincRNA-p21 expression in HK-2 cells, followed by evaluation of cellular inflammation, endoplasmic reticulum (ER) stress and apoptosis by qRT-PCR after PA exposure. Western blot and ELISA were performed to investigate the associated signaling cascades.
Results
Compared with ND-fed mice, a significantly increase in the expression of lincRNA-p21 was found in kidney biopsy from HFD-fed mice. Consistently, markedly upregulated expression of lincRNA-p21was observed in PA-treated HK-2 cells. By contrast, silencing lincRNA-p21significantly counteracted PA-induced gene expression associated with inflammation (IL6), ER stress (BiP, sXBP1 and CHOP) and apoptosis (BCL2). Additionally, PA suppressed PI3K/Akt/mTOR/Mdm2 signaling cascades and subsequently led to enhanced p53 activity, which consequently drove lincRNA-p21 expression in HK-2 cells.
Conclusion
PA acts through PI3K/Akt/mTOR/Mdm2 signaling pathway to up-regulate lincRNA-p21 expression in a p53-dependent manner, thereby contributing to lipotoxicity-induced pathological process in HK-2 cells.
Funding: National Natural Science Foundation of China (81870496), Hong Kong Research Grants Council Collaborative Research Fund (C7018-16G) and Hong Kong Society of Nephrology Research Grant (2018)
Funding
- Government Support - Non-U.S.