PMID- 29105510
OWN - NLM
STAT- MEDLINE
DCOM- 20180817
LR  - 20181113
IS  - 1535-3699 (Electronic)
IS  - 1535-3702 (Print)
IS  - 1535-3699 (Linking)
VI  - 243
IP  - 1
DP  - 2018 Jan
TI  - MicroRNA-29a mitigation of endoplasmic reticulum and autophagy aberrance 
      counteracts in obstructive jaundice-induced fibrosis in mice.
PG  - 13-21
LID - 10.1177/1535370217741500 [doi]
AB  - Hepatic fibrosis was caused by a number of signaling pathways that damage liver 
      integrity. We have previously shown that microRNA-29a (miR-29a) protects against 
      liver fibrosis. Aberrant endoplasmic reticulum (ER) and autophagy function 
      reportedly exaggerate hepatic disorders. The aim of this study was to 
      characterize the biological influence of miR-29a on ER function in injured livers 
      with bile duct ligation (BDL). We performed BDL on miR-29a transgenic mice 
      (miR-29aTg) and wild-type mice to induce cholestatic liver injury. Rat T6 cells 
      were transfected with miR-29a mimic and tunicamycin. Compared to the wild-type 
      mice, the BDL deterioration of liver function in terms of total bilirubin, 
      alanine transaminase, and aspartate transaminase activity in the miR-29aTg mice 
      was significantly reduced. Affected livers in the miR-29aTg mice demonstrated a 
      slight fibrotic matrix formation. miR-29a over-expression reduced the BDL 
      disturbance of the expressions of inositol-requiring kinase 1alpha, 
      double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase, 
      spliced-X-box binding protein 1 (sXBP1), CCAAT/enhancer-binding protein 
      homologous protein (CHOP), ULK, LC3BII, p62, and cleaved caspase-8, 9 and 3. In 
      vitro, T6 cells exposed to tunicamycin by increasing abundances of CHOP, sXBP1, 
      cleaved caspase-3, and LC3BII were diminished in the cell cultures transfected 
      with the miR-29a mimic. On the other hand, we observed that miR-29a signaling 
      protected liver tissues from BDL-mediated metabolic dysfunction and excessive 
      fibrosis histopathology. This study provides new molecular insight into the 
      miR-29a stabilization of ER integrity that slows the progression of cholestatic 
      liver deterioration. Impact statement Long-term hepatic damage caused by 
      hepatitis and cholestasis can accelerate fibrosis matrix over-production, which 
      is a harmful process attributed to the dysregulation of a number of cellular and 
      molecular events. The purpose of this study is to characterize the biological 
      influence of miR-29a on endoplasmic reticulum (ER) function in bile duct ligation 
      (BDL)-injured livers. To the best of our knowledge, this report is the first 
      demonstration that miR-29a over-expression diminishes BDL provocation of ER 
      stress (unfolded protein response, UPR) effector protein expression. This work 
      also demonstrates that miR-29a decreased caspases protein expression in 
      cholestatic livers, while an increase in miR-29a function reduced sXBP1 and CHOP 
      expressions in T6 cells in mice. Analyses of this study highlight that 
      controlling miR-29a signaling can serve as an innovative strategy in the future 
      for microRNA regulation of ER homeostasis to combat cholestasis induction hepatic 
      disorders.
FAU - Huang, Ying-Hsien
AU  - Huang YH
AUID- ORCID: 0000-0002-7127-0046
AD  - 1 Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung 
      University College of Medicine, Kaohsiung 833, Taiwan.
AD  - 2 Department of Pediatrics, Chiayi Chang Gung Memorial Hospital, Puzi City 613, 
      Taiwan.
FAU - Yang, Ya-Ling
AU  - Yang YL
AD  - 3 Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang 
      Gung University College of Medicine, Kaohsiung 833, Taiwan.
FAU - Huang, Fu-Chen
AU  - Huang FC
AD  - 1 Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung 
      University College of Medicine, Kaohsiung 833, Taiwan.
FAU - Tiao, Mao-Meng
AU  - Tiao MM
AD  - 1 Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung 
      University College of Medicine, Kaohsiung 833, Taiwan.
FAU - Lin, Yen-Cheng
AU  - Lin YC
AD  - 2 Department of Pediatrics, Chiayi Chang Gung Memorial Hospital, Puzi City 613, 
      Taiwan.
FAU - Tsai, Ming-Horng
AU  - Tsai MH
AD  - 4 Department of Pediatrics, Division of Neonatology and Pediatric 
      Hematology/Oncology, Chang Gung Memorial Hospital, Yunlin 638, Taiwan.
FAU - Wang, Feng-Sheng
AU  - Wang FS
AD  - 5 Genomics and Proteomics Core Laboratory, Department of Medical Research, 
      Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of 
      Medicine, Kaohsiung 833, Taiwan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171106
PL  - Switzerland
TA  - Exp Biol Med (Maywood)
JT  - Experimental biology and medicine (Maywood, N.J.)
JID - 100973463
RN  - 0 (MIRN29 microRNA, mouse)
RN  - 0 (MicroRNAs)
SB  - IM
MH  - Animals
MH  - *Autophagy
MH  - Cell Line
MH  - Endoplasmic Reticulum/*pathology
MH  - Jaundice, Obstructive/*complications
MH  - Liver Cirrhosis/*pathology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - MicroRNAs/*metabolism
MH  - Rats
PMC - PMC5788159
OTO - NOTNLM
OT  - MicroRNA-29a
OT  - autophagy
OT  - bile duct ligation
OT  - cholestasis
OT  - endoplasmic reticulum stress
OT  - liver fibrosis
EDAT- 2017/11/07 06:00
MHDA- 2018/08/18 06:00
PMCR- 2018/07/01
CRDT- 2017/11/07 06:00
PHST- 2017/11/07 06:00 [pubmed]
PHST- 2018/08/18 06:00 [medline]
PHST- 2017/11/07 06:00 [entrez]
PHST- 2018/07/01 00:00 [pmc-release]
AID - 10.1177_1535370217741500 [pii]
AID - 10.1177/1535370217741500 [doi]
PST - ppublish
SO  - Exp Biol Med (Maywood). 2018 Jan;243(1):13-21. doi: 10.1177/1535370217741500. 
      Epub 2017 Nov 6.