New Mutation of Coenzyme Q10 Monooxygenase 6 Causing Podocyte Injury in a Focal Segmental Glomerulosclerosis Patient  

作　　者：Cheng-Cheng Song Quan Hong Xiao-Dong Geng Xu Wang Shu-Qiang Wang Shao-Yuan Cui Man-Di Guo Ou Li Guang-Yan Cai Xiang-Mei Chen Di Wu 

机构地区：[1]Department of Nephrology,Chinese People's Liberation Army General Hospital,Chinese People's Liberation Army Institute of Nephrology,State Key Laboratory of Kidney Diseases (2011DAV00088),National Clinical Research Center for Kidney Diseases,Beijing Key Laboratory of Kidney Diseases,Beijing 100853,China

出　　处：《Chinese Medical Journal》2018年第22期2666-2675,共10页中华医学杂志（英文版）

摘　　要：Background:Focal segmental glomerulosclerosis (FSGS)is a kidney disease that is commonly associated with proteinuria and the progressive loss of renal function,which is characterized by podocyte injury and the depletion and collapse of glomerular capillary segments.The pathogenesis of FSGS has not been completely elucidated;however,recent advances in molecular genetics have provided increasing evidence that podocyte structural and functional disruption is central to FSGS pathogenesis.Here,we identified a patient with FSGS and aimed to characterize the pathogenic gene and verify its mechanism. Methods:Using next-generation sequencing and Sanger sequencing,we screened the causative gene that was linked to FSGS in this study.The patient's total blood RNA was extracted to validate the messenger RNA (mRNA)expression of coenzyme Q10 monooxygenase 6(COQ6)and validated it by immunohistochemistry.COQ6 knockdown in podocytes was performed in vitro with small interfering RNA, and then,F-actin was determined using immunofluorescence staining.Cell apoptosis was evaluated by flow cytometry,the expression of active caspase-3was determined by Western blot,and mitochondrial function was detected by MitoSOX. Results:Using whole-exome sequencing and Sanger sequencing,we screened a new causative gene,COQ6,NM_182480:exonl:c.G41A: p.W14X.The mRNA expression of COQ6 in the proband showed decreased.Moreover,the expression of COQ6,which was validated by immunohistochemistry,also had the same change in the proband.Finally,we focused on the COQ6 gene to clarify the mechanism of podocyte injury.Flow cytometry showed significantly increased in apoptotic podocytes,and Western blotting showed increases in active caspase-3in si-COQ6 podocytes.Meanwhile,reactive oxygen species (ROS)levels were increased and F-actin immunofluorescence was irregularly distributed in the si-COQ6 group. Conclusions:This study reported a possible mechanism for FSGS and suggested that a new mutation in COQ6,which could cause respiratory chain defect,increase the gener

关 键 词：Apoptosis COENZYME Q10 MONOOXYGENASE 6 Mutation Focal SEGMENTAL GLOMERULOSCLEROSIS PODOCYTE 

分 类 号：R[医药卫生]