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Int J Biol Sci 2023; 19(5):1633-1644. doi:10.7150/ijbs.77153 This issue Cite

Research Paper

Parkin increases the risk of colitis by downregulation of VDR via autophagy-lysosome degradation

Zemeng Ma1,#, Junxian Wu1,#, Yuqing Wu1,5,6,#, Xiaomeng Sun1,#, Zebing Rao1,#, Naishuang Sun1, Yu Fu7,8, Zaikui Zhang1, Jingzhou Li1, Mengjun Xiao1, Qiang Zeng1, Yuxuan Wu1, Chenhua Han1, Ding Ding1, Hongjie Zhang4, Hua Yuan7,8, Jing zhang3,✉, Shuo Yang1,✉, Yunzi Chen1,2✉

1. Key Laboratory of Immune Microenvironment and Disease, Department of Immunology, Nanjing Medical University, Nanjing211166, China.
2. Medical Centre for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing 211166, China.
3. The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China.
4. Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 211166, China.
5. Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing211166, China.
6. National Key Clinical Department of Laboratory Medicine, Nanjing 210029, China.
7. Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.
8. Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
#These authors have contributed equally to this work

✉ Corresponding authors: chenyunziedu.cn (Y.C.), shuoyangedu.cn (S.Y.), jzhang08edu.cn (J.Z.)

Citation:
Ma Z, Wu J, Wu Y, Sun X, Rao Z, Sun N, Fu Y, Zhang Z, Li J, Xiao M, Zeng Q, Wu Y, Han C, Ding D, Zhang H, Yuan H, zhang J, Yang S, Chen Y. Parkin increases the risk of colitis by downregulation of VDR via autophagy-lysosome degradation. Int J Biol Sci 2023; 19(5):1633-1644. doi:10.7150/ijbs.77153. https://www.ijbs.com/v19p1633.htm
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Abstract

Graphic abstract

Parkin, an E3 ubiquitin ligase, plays an essential role in mitophagy. Emerging evidence indicates that mitophagy is involved in various processes closely related to immune diseases, including inflammatory bowel diseases (IBD). Here, the authors show that Parkin increases the occurrence of colitis and severe inflammation. Deletion of Parkin resulted in marked reductions in colonic inflammation and exhibited high resistance to DSS-induced colitis. Mechanism investigation indicated that Parkin interacts with Vitamin D receptors (VDR), a critical inhibitory regulator in IBD. Parkin promotes VDR degradation via the p62-related autophagy-lysosome pathway. Comparison of colitis in Parkin-/- and Parkin-/-Vdr-/- mice showed that the protective effect of Parkin deletion against colitis was abolished by VDR deletion. The result suggests that the regulatory effect of Parkin in colitis is a VDR-dependent pathway. Our research provides a new role of Parkin in colitis by downregulating VDR, which provides a potential strategy for treating IBD.

Keywords: Parkin, Vitamin D receptors, inflammatory bowel diseases

Citation styles

APA
Ma, Z., Wu, J., Wu, Y., Sun, X., Rao, Z., Sun, N., Fu, Y., Zhang, Z., Li, J., Xiao, M., Zeng, Q., Wu, Y., Han, C., Ding, D., Zhang, H., Yuan, H., zhang, J., Yang, S., Chen, Y. (2023). Parkin increases the risk of colitis by downregulation of VDR via autophagy-lysosome degradation. International Journal of Biological Sciences, 19(5), 1633-1644. https://doi.org/10.7150/ijbs.77153.

ACS
Ma, Z.; Wu, J.; Wu, Y.; Sun, X.; Rao, Z.; Sun, N.; Fu, Y.; Zhang, Z.; Li, J.; Xiao, M.; Zeng, Q.; Wu, Y.; Han, C.; Ding, D.; Zhang, H.; Yuan, H.; zhang, J.; Yang, S.; Chen, Y. Parkin increases the risk of colitis by downregulation of VDR via autophagy-lysosome degradation. Int. J. Biol. Sci. 2023, 19 (5), 1633-1644. DOI: 10.7150/ijbs.77153.

NLM
Ma Z, Wu J, Wu Y, Sun X, Rao Z, Sun N, Fu Y, Zhang Z, Li J, Xiao M, Zeng Q, Wu Y, Han C, Ding D, Zhang H, Yuan H, zhang J, Yang S, Chen Y. Parkin increases the risk of colitis by downregulation of VDR via autophagy-lysosome degradation. Int J Biol Sci 2023; 19(5):1633-1644. doi:10.7150/ijbs.77153. https://www.ijbs.com/v19p1633.htm

CSE
Ma Z, Wu J, Wu Y, Sun X, Rao Z, Sun N, Fu Y, Zhang Z, Li J, Xiao M, Zeng Q, Wu Y, Han C, Ding D, Zhang H, Yuan H, zhang J, Yang S, Chen Y. 2023. Parkin increases the risk of colitis by downregulation of VDR via autophagy-lysosome degradation. Int J Biol Sci. 19(5):1633-1644.

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