PMID- 30880031
OWN - NLM
STAT- MEDLINE
DCOM- 20200526
LR  - 20211204
IS  - 1090-2422 (Electronic)
IS  - 0014-4827 (Linking)
VI  - 378
IP  - 2
DP  - 2019 May 15
TI  - Human umbilical cord-derived mesenchymal stem cells enhanced HK-2 cell autophagy 
      through MicroRNA-145 by inhibiting the PI3K/AKT/mTOR signaling pathway.
PG  - 198-205
LID - S0014-4827(18)31047-4 [pii]
LID - 10.1016/j.yexcr.2019.03.019 [doi]
AB  - Recent studies have shown that autophagy exhibits a protective role in acute 
      kidney injury (AKI), and the accumulation of advanced oxidation protein products 
      (AOPP) participates in the progression of kidney diseases. Our previous study 
      indicated that AOPP induced injury in renal tubular epithelial cells (RTECs) 
      through autophagy inhibition. Besides, we found that human umbilical cord-derived 
      mesenchymal stem cells (hUC-MSCs) enhanced autophagy in AOPP-treated RTECs, but 
      the underlying mechanism remains unclear. We regulated microRNA-145 (miR-145) 
      expression in HK-2 cells (a cell line of RTECs), or co-cultured hUC-MSCs with 
      HK-2 cells and studied the autophagic activity in HK-2 cells to explore the 
      underlying mechanism. Our data demonstrated that upregulated miR-145 increased 
      LC3 II and Beclin 1 levels, decreased p62 level, three autophagy related 
      proteins, inhibited the phosphorylation of PI3K/AKT/mTOR, and increased 
      LC3B-positive staining and the autophagosome number. Furthermore, hUC-MSCs 
      enhanced autophagy and inhibited phosphorylation of PI3K/AKT/mTOR in AOPP-treated 
      HK-2 cells, which was then partially rescued using miR-145 knockdown in the 
      hUC-MSCs co-culture system. In conclusion, our study showed that hUC-MSCs 
      enhanced autophagy in AOPP-treated HK-2 cells mediated by miR-145 via inhibition 
      of the PI3K/AKT/mTOR pathway, which indicated that hUC-MSCs might serve as a 
      prospective therapy for AKI.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Xiang, Jin
AU  - Xiang J
AD  - Department of Nephrology, Zhujiang Hospital of Southern Medical University, 
      Guangzhou, Guangdong Province, 510282, China; Department of Nephrology, People's 
      Hospital of Yuxi City, Yuxi, Yunnan Province, 653100, China.
FAU - Jiang, Tingting
AU  - Jiang T
AD  - Department of Nephrology, The People's Hospital of Guangxi Zhuang Autonomous 
      Region, Nanning, Guangxi Province, 530021, China.
FAU - Zhang, Wenying
AU  - Zhang W
AD  - Department of Nephrology, Zhujiang Hospital of Southern Medical University, 
      Guangzhou, Guangdong Province, 510282, China.
FAU - Xie, Wei
AU  - Xie W
AD  - Department of Nephrology, Zhujiang Hospital of Southern Medical University, 
      Guangzhou, Guangdong Province, 510282, China.
FAU - Tang, Xun
AU  - Tang X
AD  - Department of Nephrology, Zhujiang Hospital of Southern Medical University, 
      Guangzhou, Guangdong Province, 510282, China. Electronic address: 
      1847672118@qq.com.
FAU - Zhang, Jun
AU  - Zhang J
AD  - Department of Nephrology, Zhujiang Hospital of Southern Medical University, 
      Guangzhou, Guangdong Province, 510282, China. Electronic address: gzh_zj@qq.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190314
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Advanced Oxidation Protein Products)
RN  - 0 (MIRN145 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Advanced Oxidation Protein Products/physiology
MH  - Autophagy/*physiology
MH  - Cell Line
MH  - Coculture Techniques
MH  - Humans
MH  - Kidney Tubules/*cytology
MH  - Mesenchymal Stem Cells/metabolism/*physiology
MH  - MicroRNAs/*metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Umbilical Cord/cytology
MH  - Urothelium/metabolism/*physiology
OTO - NOTNLM
OT  - Autophagy
OT  - HK-2 cells
OT  - PI3K/AKT/mTOR
OT  - hUC-MSCs
OT  - miR-145
EDAT- 2019/03/19 06:00
MHDA- 2020/05/27 06:00
CRDT- 2019/03/19 06:00
PHST- 2018/10/02 00:00 [received]
PHST- 2019/03/10 00:00 [revised]
PHST- 2019/03/11 00:00 [accepted]
PHST- 2019/03/19 06:00 [pubmed]
PHST- 2020/05/27 06:00 [medline]
PHST- 2019/03/19 06:00 [entrez]
AID - S0014-4827(18)31047-4 [pii]
AID - 10.1016/j.yexcr.2019.03.019 [doi]
PST - ppublish
SO  - Exp Cell Res. 2019 May 15;378(2):198-205. doi: 10.1016/j.yexcr.2019.03.019. Epub 
      2019 Mar 14.