PMID- 26414307
OWN - NLM
STAT- MEDLINE
DCOM- 20160318
LR  - 20230216
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Linking)
VI  - 95
IP  - 12
DP  - 2015 Dec
TI  - The roles of oxidative stress, endoplasmic reticulum stress, and autophagy in 
      aldosterone/mineralocorticoid receptor-induced podocyte injury.
PG  - 1374-86
LID - 10.1038/labinvest.2015.118 [doi]
AB  - Podocytes play an important role in the pathogenesis and progression of 
      glomerulosclerosis. Recent studies indicate that aldosterone/mineralocorticoid 
      receptor (MR) is a major contributor of chronic kidney disease (CKD) progression. 
      Aldosterone/MR induces glomerular podocyte injury, causing the disruption of the 
      glomerular filtration barrier and proteinuria. The present study investigated the 
      mechanisms by which aldosterone/MR mediated podocyte injury, focusing on the 
      involvement of oxidative stress, endoplasmic reticulum (ER) stress, and 
      autophagy. We observed that aldosterone/MR induced ER stress and podocyte injury 
      both in vivo and in vitro. Blockade of ER stress significantly reduced 
      aldosterone/MR-induced podocyte injury. In addition, we found that ER 
      stress-induced podocyte injury was mediated by CCAAT/enhancer-binding protein 
      (C/EBP) homologous protein (Chop). Interestingly, autophagy was also enhanced by 
      aldosterone/MR. Pharmacological inhibition of autophagy resulted in increased 
      apoptosis. Inhibition of ER stress significantly reduced aldosterone/MR-induced 
      autophagy. In addition, the activation of ER stress increased the formation of 
      autophagy, which protected podocytes from apoptosis. Moreover, we observed that 
      the addition of ROS scavenger, N-acetyl cystein (NAC), blocked both ER stress and 
      autophagy by aldosterone/MR. Collectively, these results suggest that oxidant 
      stress-mediated aldosterone/MR-induced podocyte injury via activating ER stress, 
      which then triggers both Chop-dependent apoptosis and autophagy to cope with the 
      injury. These findings may guide us to therapeutic strategies for glomerular 
      diseases.
FAU - Yuan, Yanggang
AU  - Yuan Y
AD  - Department of Nephrology, the First Affiliated Hospital of Nanjing Medical 
      University, Jiangsu Province Hospital, Nanjing, China.
FAU - Xu, Xueqiang
AU  - Xu X
AD  - Department of Nephrology, the First Affiliated Hospital of Nanjing Medical 
      University, Jiangsu Province Hospital, Nanjing, China.
FAU - Zhao, Chuanyan
AU  - Zhao C
AD  - Department of Nephrology, the First Affiliated Hospital of Nanjing Medical 
      University, Jiangsu Province Hospital, Nanjing, China.
FAU - Zhao, Min
AU  - Zhao M
AD  - Department of Nephrology, Nanjing Children's Hospital, Nanjing Medical 
      University, Nanjing, China.
AD  - Institute of Pediatrics, Nanjing Medical University, Nanjing, China.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Nephrology, the First Affiliated Hospital of Nanjing Medical 
      University, Jiangsu Province Hospital, Nanjing, China.
FAU - Zhang, Bo
AU  - Zhang B
AD  - Department of Nephrology, the First Affiliated Hospital of Nanjing Medical 
      University, Jiangsu Province Hospital, Nanjing, China.
FAU - Wang, Ningning
AU  - Wang N
AD  - Department of Nephrology, the First Affiliated Hospital of Nanjing Medical 
      University, Jiangsu Province Hospital, Nanjing, China.
FAU - Mao, Huijuan
AU  - Mao H
AD  - Department of Nephrology, the First Affiliated Hospital of Nanjing Medical 
      University, Jiangsu Province Hospital, Nanjing, China.
FAU - Zhang, Aihua
AU  - Zhang A
AD  - Department of Nephrology, Nanjing Children's Hospital, Nanjing Medical 
      University, Nanjing, China.
AD  - Institute of Pediatrics, Nanjing Medical University, Nanjing, China.
FAU - Xing, Changying
AU  - Xing C
AD  - Department of Nephrology, the First Affiliated Hospital of Nanjing Medical 
      University, Jiangsu Province Hospital, Nanjing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150928
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Ddit3 protein, mouse)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, Mineralocorticoid)
RN  - 147336-12-7 (Transcription Factor CHOP)
RN  - 4964P6T9RB (Aldosterone)
SB  - IM
MH  - Aldosterone/*metabolism
MH  - Animals
MH  - *Autophagy
MH  - Cells, Cultured
MH  - *Endoplasmic Reticulum Stress
MH  - Kidney Diseases/*etiology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - *Oxidative Stress
MH  - Podocytes/*physiology
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, Mineralocorticoid/metabolism
MH  - Transcription Factor CHOP/metabolism
EDAT- 2015/09/29 06:00
MHDA- 2016/03/19 06:00
CRDT- 2015/09/29 06:00
PHST- 2014/10/28 00:00 [received]
PHST- 2015/07/08 00:00 [revised]
PHST- 2015/07/13 00:00 [accepted]
PHST- 2015/09/29 06:00 [entrez]
PHST- 2015/09/29 06:00 [pubmed]
PHST- 2016/03/19 06:00 [medline]
AID - S0023-6837(22)01389-7 [pii]
AID - 10.1038/labinvest.2015.118 [doi]
PST - ppublish
SO  - Lab Invest. 2015 Dec;95(12):1374-86. doi: 10.1038/labinvest.2015.118. Epub 2015 
      Sep 28.