Theranostics 2022; 12(8):3896-3910. doi:10.7150/thno.72515 This issue
1. Tongji School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, 430030.
2. Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology and Metabolism, College of Life Sciences, Wuhan University, Wuhan, China, 430072.
3. Department of Transfusion Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, 430030.
4. Department of Pathology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, 430030.
5. Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, 430030.
Rationale: Ischemia-reperfusion (IR) induced acute kidney injury (AKI) causes serious clinical problems associated with high morbidity and mortality. Mecp2 is a methyl-CpG binding protein, its mutation or deletion causes a neurodevelopment disease called Rett syndrome. Notably, some Rett syndrome patients present urological dysfunctions. It remains unclear whether and how Mecp2 affects AKI.
Methods: Renal tubular cell specific Mecp2 deletion mice challenged with IR injury were used to investigate the effects of Mecp2 on renal tubular damage, function, cell death, fibrosis and inflammation. Cultured renal epithelial cell lines were transfected with wildtype or different domain-deletion mutants of Mecp2 to study the effects of Mecp2 on Il-6/STAT3 signaling.
Results: Our results indicated rapidly upregulated Mecp2 upon acute in vivo and in vitro renal injury. Notably, increased tubular MeCP2 staining was also found in the renal sections of AKI patients. Furthermore, ablation of Mecp2 aggravated renal injury, and promoted renal cell death, inflammation, and fibrosis. Mechanistically, through its transcriptional repression domain, Mecp2 bound to the promoter of proinflammatory cytokine Il-6 to negatively regulate its expression, thus inhibiting STAT3 activation.
Conclusions: A novel protective role of Mecp2 against AKI via repressing the Il-6/STAT3 axis was suggested.
Keywords: renal ischemia-reperfusion, Mecp2, inflammation, IL-6/STAT3 signaling, fibrosis