title: RhoA deficiency disrupts podocyte cytoskeleton and induces podocyte apoptosis by inhibiting YAP/dendrin signal.
abstract: Podocyte apoptosis is a major mechanism that leads to proteinuria in many kidney diseases. However, the concert mechanisms that cause podocyte apoptosis in these kidney diseases are not fully understood. RhoA is one of Rho GTPases that has been well studied and plays a key role in regulating cytoskeletal architecture. Previous study showed that insufficient RhoA could result in rat aortic smooth muscle cell apoptosis. However, whether RhoA is involved in podocyte apoptosis remains unknown.
  
  
  
  Culture podocytes were treated with LPS, ADR or siRNA for 48 h before harvest. Subcellular immunoblotting, qRT-PCR, immunofluorescence and flow cytometry were used to exam the expression and function of RhoA or YAP in podocytes.
  
  
  
  We found that the expression of RhoA and its activity were significantly decreased in LPS or ADR-injured podocytes, accompanying loss of stress fibers and increased cell apoptosis. Knocking down RhoA or its downstream effector mDia expression by siRNA also caused loss of stress fibers and podocyte apoptosis. Moreover, our results further demonstrated that RhoA deficiency could reduce the mRNA and protein expression of YAP, which had been regarded as an anti-apoptosis protein in podocyte. Silenced dendrin expression significantly abolished RhoA, mDia or YAP deficiency-induced podocyte apoptosis.
  
  
  
  RhoA deficiency could disrupt podocyte cytoskeleton and induce podocyte apoptosis by inhibiting YAP/dendrin signal. RhoA/mDia/YAP/dendrin signal pathway may potentially play an important role in regulating podocyte apoptosis. Maintaining necessary RhoA would be one potent way to prevent proteinuria kidney diseases.
authors.affiliation: Division of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080, China.|Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Zongshun
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Division of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Division of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080, China.
authors.forename: Yuanhan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Division of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080, China.
authors.forename: Chunping
authors.initials: C
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, China.|Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, China.
authors.forename: Fangjian
authors.initials: F
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, China.|Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, China.
authors.forename: Zhiling
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, China.|Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Division of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080, China.
authors.forename: Ruizhao
authors.initials: R
authors.lastname: Li
authors.affiliation: Division of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080, China.
authors.forename: Jianchao
authors.initials: J
authors.lastname: Ma
authors.affiliation: Division of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Li
authors.affiliation: Division of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080, China.
authors.forename: Yuxiong
authors.initials: Y
authors.lastname: Lai
authors.affiliation: Division of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Lin
authors.affiliation: Division of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080, China.
authors.forename: Xinchen
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Division of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080, China.
authors.forename: Qianmei
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Division of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Division of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Division of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080, China.
authors.forename: Shuangxin
authors.initials: S
authors.lastname: Liu
authors.affiliation: Division of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080, China.
authors.forename: Wenjian
authors.initials: W
authors.lastname: Wang
authors.affiliation: Division of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080, China.
authors.forename: Xinling
authors.initials: X
authors.lastname: Liang
authors.affiliation: Division of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080, China.
authors.forename: Ruyi
authors.initials: R
authors.lastname: Liao
authors.affiliation: Division of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080, China. shiweigd@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D002460:Cell Line; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D004317:Doxorubicin / Q000494:pharmacology; D000080865:Formins; D020868:Gene Silencing; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D050199:Podocytes / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D022502:Stress Fibers / Q000187:drug effects / Q000648:ultrastructure; D000091102:YAP-Signaling Proteins; D020742:rhoA GTP-Binding Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000903:Antibiotics, Antineoplastic; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C491464:Diap1 protein, mouse; D000080865:Formins; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; C104328:dendrin; D004317:Doxorubicin; D020742:rhoA GTP-Binding Protein
keywords: Apoptosis; Dendrin; RhoA; Stress fibers; YAP; mDia