PMID- 29367621
OWN - NLM
STAT- MEDLINE
DCOM- 20190612
LR  - 20201209
IS  - 2041-4889 (Electronic)
VI  - 9
IP  - 2
DP  - 2018 Jan 24
TI  - Optineurin-mediated mitophagy protects renal tubular epithelial cells against 
      accelerated senescence in diabetic nephropathy.
PG  - 105
LID - 10.1038/s41419-017-0127-z [doi]
LID - 105
AB  - Premature senescence is a key process in the progression of diabetic nephropathy 
      (DN). Premature senescence of renal tubular epithelial cells (RTEC) in DN may 
      result from the accumulation of damaged mitochondria. Mitophagy is the principal 
      process that eliminates damaged mitochondria through PTEN-induced putative kinase 
      1 (PINK1)-mediated recruitment of optineurin (OPTN) to mitochondria. We aimed to 
      examine the involvement of OPTN in mitophagy regulation of cellular senescence in 
      RTEC in the context of DN. In vitro, the expression of senescence markers P16, 
      P21, DcR2, SA-beta-gal, SAHF, and insufficient mitophagic degradation marker 
      (mitochondrial P62) in mouse RTECs increased after culture in 30 mM high-glucose 
      (HG) conditions for 48 h. Mitochondrial fission/mitophagy inhibitor Mdivi-1 
      significantly enhanced RTEC senescence under HG conditions, whereas 
      autophagy/mitophagy agonist Torin1 inhibited cell senescence. MitoTempo inhibited 
      HG-induced mitochondrial reactive oxygen species and cell senescence with or 
      without Mdivi-1. The expression of PINK1 and OPTN, two regulatory factors for 
      mitophagosome formation, decreased significantly after HG stimulation. 
      Overexpression of PINK1 did not enhance mitophagosome formation under HG 
      conditions. OPTN silencing significantly inhibited HG-induced mitophagosome 
      formation, and overexpression of OPTN relieved cellular senescence through 
      promoting mitophagy. In clinical specimens, renal OPTN expression was gradually 
      decreased with increased tubulointerstitial injury scores. OPTN-positive renal 
      tubular cells did not express senescence marker P16. OPTN expression also 
      negatively correlated with serum creatinine levels, and positively correlated 
      with eGFR. Thus, OPTN-mediated mitophagy plays a crucial regulatory role in 
      HG-induced RTEC senescence in DN. OPTN may, therefore, be a potential 
      antisenescence factor in DN.
FAU - Chen, Kehong
AU  - Chen K
AD  - Department of Nephrology, Daping Hospital, Research Institute of Surgery, Third 
      Military Medical University, Chongqing, PR China.
FAU - Dai, Huanzi
AU  - Dai H
AD  - Department of Nephrology, Daping Hospital, Research Institute of Surgery, Third 
      Military Medical University, Chongqing, PR China.
FAU - Yuan, Junjie
AU  - Yuan J
AD  - Department of Nephrology, Daping Hospital, Research Institute of Surgery, Third 
      Military Medical University, Chongqing, PR China.
FAU - Chen, Jia
AU  - Chen J
AD  - Department of Nephrology, Daping Hospital, Research Institute of Surgery, Third 
      Military Medical University, Chongqing, PR China.
FAU - Lin, Lirong
AU  - Lin L
AD  - Department of Nephrology, Daping Hospital, Research Institute of Surgery, Third 
      Military Medical University, Chongqing, PR China.
FAU - Zhang, Weiwei
AU  - Zhang W
AD  - Department of Nephrology, Daping Hospital, Research Institute of Surgery, Third 
      Military Medical University, Chongqing, PR China.
FAU - Wang, Limin
AU  - Wang L
AD  - Department of Nephrology, Daping Hospital, Research Institute of Surgery, Third 
      Military Medical University, Chongqing, PR China.
FAU - Zhang, Jianguo
AU  - Zhang J
AD  - Department of Nephrology, Daping Hospital, Research Institute of Surgery, Third 
      Military Medical University, Chongqing, PR China.
FAU - Li, Kailong
AU  - Li K
AD  - Department of Nephrology, Daping Hospital, Research Institute of Surgery, Third 
      Military Medical University, Chongqing, PR China.
FAU - He, Yani
AU  - He Y
AD  - Department of Nephrology, Daping Hospital, Research Institute of Surgery, Third 
      Military Medical University, Chongqing, PR China. heynmail@yahoo.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180124
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Eye Proteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (OPTN protein, human)
RN  - 0 (Optn protein, mouse)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Transcription Factor TFIIIA)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (PTEN-induced putative kinase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Cell Cycle Proteins
MH  - *Cellular Senescence
MH  - *Cytoprotection
MH  - Diabetic Nephropathies/*pathology
MH  - Disease Progression
MH  - Epithelial Cells/metabolism/*pathology/ultrastructure
MH  - Eye Proteins/*metabolism
MH  - Glucose/toxicity
MH  - Humans
MH  - Kidney Tubules/*pathology
MH  - Membrane Transport Proteins
MH  - Mice, Inbred C57BL
MH  - Mitochondria/drug effects/metabolism/pathology/ultrastructure
MH  - *Mitophagy
MH  - Phagosomes/drug effects/metabolism/ultrastructure
MH  - Protein Kinases/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Transcription Factor TFIIIA/*metabolism
PMC - PMC5833650
COIS- The authors declare that they have no conflict of interest.
EDAT- 2018/01/26 06:00
MHDA- 2019/06/14 06:00
PMCR- 2018/01/24
CRDT- 2018/01/26 06:00
PHST- 2017/07/29 00:00 [received]
PHST- 2017/11/06 00:00 [accepted]
PHST- 2017/11/03 00:00 [revised]
PHST- 2018/01/26 06:00 [entrez]
PHST- 2018/01/26 06:00 [pubmed]
PHST- 2019/06/14 06:00 [medline]
PHST- 2018/01/24 00:00 [pmc-release]
AID - 10.1038/s41419-017-0127-z [pii]
AID - 127 [pii]
AID - 10.1038/s41419-017-0127-z [doi]
PST - epublish
SO  - Cell Death Dis. 2018 Jan 24;9(2):105. doi: 10.1038/s41419-017-0127-z.