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Kidney Week

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.