PMID- 32092824
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210110
IS  - 2162-2531 (Print)
IS  - 2162-2531 (Electronic)
IS  - 2162-2531 (Linking)
VI  - 19
DP  - 2020 Mar 6
TI  - Upregulation of miR-101a Suppresses Chronic Renal Fibrosis by Regulating KDM3A 
      via Blockade of the YAP-TGF-beta-Smad Signaling Pathway.
PG  - 1276-1289
LID - S2162-2531(20)30036-6 [pii]
LID - 10.1016/j.omtn.2020.01.002 [doi]
AB  - Renal fibrosis denotes a common complication of diabetic nephropathy and is a 
      predominant cause of end-stage renal disease. Despite the association between 
      microRNAs (miRNAs or miRs) and renal fibrosis, miRNAs have been reported to play 
      a vital role in the development of chronic renal fibrosis. Therefore, the aim of 
      the present study was to investigate the possible function of miR-101a in chronic 
      renal fibrosis. Initially, microarray-based gene expression profiling of renal 
      fibrosis was employed to screen the differentially expressed genes. An in vivo 
      mouse model of chronic renal fibrosis induced by a unilateral ureteral 
      obstruction (UUO) and an in vitro cell model induced by aristolochic acid (AA) 
      were constructed. miR-101a expression was examined using a fluorescence in situ 
      hybridization (FISH) assay and quantitative reverse transcription polymerase 
      chain reaction (qRT-PCR). Then, the interaction between miR-101a and KDM3A was 
      identified using an online website combined with a dual-luciferase reporter 
      assay. Finally, gain- and loss-of-function experiments were conducted to 
      elucidate the effect of miR-101a on the expression of Col1a1, fibronectin, 
      alpha-smooth muscle actin (alpha-SMA), and YAP-TGF-beta (transforming growth factor beta)-Smad 
      signaling pathway-related genes, as well as the degree of renal fibrosis. 
      miR-101a was poorly expressed while KDM3A was robustly induced in chronic renal 
      fibrosis tissues and cells. In addition, miR-101a could target and downregulate 
      KDM3A expression, which led to elevated TGIF1, inhibited expression of Collagen I 
      (Col1a1), fibronectin, alpha-SMA, YAP1, and TGF-beta2 along with the extent of Smad2/3 
      phosphorylation, as well as delayed renal fibrosis degree. Besides, overexpressed 
      YAP/TGF-beta2 or inhibited TGIF1 partially restored the inhibitory effect of 
      miR-101a on chronic renal fibrosis. Taken together, miR-101a could potentially 
      slow down chronic renal fibrosis by the inactivation of the YAP-TGF-beta-Smad 
      signaling pathway via KDM3A, highlighting the potential of miR-101a as a 
      therapeutic target for chronic renal fibrosis treatment.
CI  - Copyright (c) 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Ding, Hong
AU  - Ding H
AD  - Department of Nephrology, The Forth Affiliated Hospital, China Medical 
      University, Shenyang 110032, Liaoning Province, P.R. China. Electronic address: 
      dinghong9209@126.com.
FAU - Xu, Yanyan
AU  - Xu Y
AD  - Department of Nephrology, The Forth Affiliated Hospital, China Medical 
      University, Shenyang 110032, Liaoning Province, P.R. China.
FAU - Jiang, Nan
AU  - Jiang N
AD  - Department of Nephrology, The Forth Affiliated Hospital, China Medical 
      University, Shenyang 110032, Liaoning Province, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20200116
PL  - United States
TA  - Mol Ther Nucleic Acids
JT  - Molecular therapy. Nucleic acids
JID - 101581621
PMC - PMC7033461
OTO - NOTNLM
OT  - KDM3A
OT  - TGIF1
OT  - YAP-TGF-beta-Smad signaling pathway
OT  - chronic renal fibrosis
OT  - enhancer
OT  - microRNA-101a
EDAT- 2020/02/26 06:00
MHDA- 2020/02/26 06:01
PMCR- 2020/01/16
CRDT- 2020/02/26 06:00
PHST- 2019/09/24 00:00 [received]
PHST- 2019/12/25 00:00 [revised]
PHST- 2020/01/02 00:00 [accepted]
PHST- 2020/02/26 06:00 [pubmed]
PHST- 2020/02/26 06:01 [medline]
PHST- 2020/02/26 06:00 [entrez]
PHST- 2020/01/16 00:00 [pmc-release]
AID - S2162-2531(20)30036-6 [pii]
AID - 10.1016/j.omtn.2020.01.002 [doi]
PST - ppublish
SO  - Mol Ther Nucleic Acids. 2020 Mar 6;19:1276-1289. doi: 10.1016/j.omtn.2020.01.002. 
      Epub 2020 Jan 16.