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RNA-binding protein,human antigen R regulates hypoxia-induced autophagy by targeting ATG7/ATG16L1 expressions and autophagosome formation |
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| Authors: | Kalaiselvi Palanisamy Tsung-Hsun Tsai Tung-Min Yu Kuo-Ting Sun Shao-Hua Yu Feng-Yen Lin I-Kuan Wang Chi-Yuan Li |
| Institution: | 1. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
Kalaiselvi Palanisamy, Tsung-Hsun Tsai and Tung-Min Yu contributed equally to this study.;2. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan Division of Urology, Department of Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan Kalaiselvi Palanisamy, Tsung-Hsun Tsai and Tung-Min Yu contributed equally to this study.;3. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan Kalaiselvi Palanisamy, Tsung-Hsun Tsai and Tung-Min Yu contributed equally to this study.;4. Department of Pediatric Dentistry, China Medical University Hospital, Taichung, Taiwan School of Dentistry, College of Dentistry, China Medical University, Taichung, Taiwan;5. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan Department of Emergency Medicine, China Medical University Hospital, Taichung, Taiwan;6. Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan Division of Cardiology and Cardiovascular Research Center, Taipei Medical University Hospital, Taipei, Taiwan;7. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan |
| Abstract: | Autophagy, a prosurvival mechanism offers a protective role during acute kidney injury. We show novel findings on the functional role of RNA binding protein, HuR during hypoxia-induced autophagy in renal proximal tubular cells-2 (HK-2). HK-2 cells showed upregulated expressions of HuR and autophagy-related proteins such as autophagy related 7 (ATG7), autophagy related 16 like 1 (ATG16L1), and LC3II under hypoxia. Increased autophagosome formation was visualized as LC3 puncta in hypoxic cells. Further, short hairpin-RNA-mediated loss of HuR function in HK-2 cells significantly decreased ATG7 and ATG16L1 protein expressions. Bioinformatics prediction revealed HuR motif binding on the coding region of ATG7 and AU-rich element at 3′UTR ATG16L1 messnger RNA (mRNA). The RNA immunoprecipitation study showed that HuR was predominantly associated with ATG7 and ATG16L1 mRNAs under hypoxia. In addition, HuR enhanced autophagosome formation by regulating LC3II expressions. These results show that HuR regulates ATG7 and ATG16L1 expressions and thereby mediate autophagy in HK-2 cells. Importantly, HuR knockdown cells underwent apoptosis during hypoxia as observed through the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Collectively, these findings show the crucial role of HuR under hypoxia by regulating autophagy and suppressing apoptosis in renal tubular cells. |
| Keywords: | acute kidney injury (AKI) ATG (autophagy-related) proteins autophagosome autophagy HuR RNA binding protein (RBP) |