title: CXCL10 expression induced by Mxi1 inactivation induces mesangial cell apoptosis in mouse Habu nephritis.
abstract: MAX interactor 1 (Mxi1) proteins are c-myc antagonists that primarily exert their biological functions by inhibiting Myc-dependent gene transcription. In this study, Mxi1(-/-) mice were used to generate a model of mesangial proliferative glomerulonephritis for the first time. In the present study, we demonstrated that Mxi1(-/-) mice exhibited a more typical and severe pathological phenotype, which was displayed primarily as a noticeable dissolution phenotype with a higher proportion of apoptotic cells and higher chemokine CXCL10 expression during the early days of modeling, compared with wild-type mice. Additionally, we determined that IRF3-mediated TLR4 signaling was likely involved in regulating CXCL10 expression, which might participate in the mesangial dissolution process. We also found increases in CXCL10 expression, caspase 3 activation, and the proportion of apoptotic cells when Mxi1 expression was inhibited in mouse mesangial cells. Furthermore, the proportion of apoptotic cells decreased after inhibiting CXCL10 expression. Therefore, we concluded that the mesangial cell apoptosis observed in this mesangial proliferative glomerulonephritis model was related to CXCL10 expression induced by Mxi1 inactivation. This finding provides a new theoretical basis for the mechanism of mesangial proliferative glomerulonephritis progression and reveals potential intervention targets for the early treatment of this disease.
authors: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, China; Medical College, NanKai University, Tianjin, China.
authors: Lingling
authors: L
authors: Wu
authors: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, China; Medical College, NanKai University, Tianjin, China.
authors: Xiaoniao
authors: X
authors: Chen
authors: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, China.
authors: Yan
authors: Y
authors: Mei
authors: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, China.
authors: Quan
authors: Q
authors: Hong
authors: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, China.
authors: Zhe
authors: Z
authors: Feng
authors: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, China.
authors: Yang
authors: Y
authors: Lv
authors: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, China.
authors: Jun
authors: J
authors: Wen
authors: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, China.
authors: Xiaoluan
authors: X
authors: Liu
authors: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, China. Electronic address: caiguangyan@sina.com.
authors: Guangyan
authors: G
authors: Cai
authors: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, China. Electronic address: xmchen301@126.com.
authors: Xiangmei
authors: X
authors: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D053148:Caspase 3 / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000235:genetics*; D003435:Crotalid Venoms; D017353:Gene Deletion; D005786:Gene Expression Regulation; D005921:Glomerulonephritis / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology*; D008297:Male; D050527:Mesangial Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D017841:Trimeresurus; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D053148:Caspase 3; D054357:Chemokine CXCL10; D003435:Crotalid Venoms; D051197:Toll-Like Receptor 4; D025521:Tumor Suppressor Proteins; C485433:Cxcl10 protein, mouse; C512788:Mxi1 protein, mouse
keywords: Apoptosis; CXCL10; Caspase 3; Mesangial cells; Mxi1