PMID- 35226981
OWN - NLM
STAT- MEDLINE
DCOM- 20220401
LR  - 20220401
IS  - 2768-6698 (Electronic)
IS  - 2768-6698 (Linking)
VI  - 27
IP  - 2
DP  - 2022 Jan 24
TI  - Endoplasmic reticulum stress as a novel target to inhibit transdifferentiation of 
      human retinal pigment epithelial cells.
PG  - 38
LID - 10.31083/j.fbl2702038 [doi]
AB  - BACKGROUND: The epithelial to mesenchymal transition (EMT) of retinal pigment 
      epithelial (RPE) cells is a critical event in the pathogenesis of proliferative 
      vitreoretinopathy and neovascular age-related macular degeneration, which are the 
      leading causes of severe vision loss. Endoplasmic reticulum (ER) stress has been 
      implicated in the EMT of many cell types and various ocular diseases. However, 
      the relationship between ER stress and EMT in RPE cells remains unknown. 
      Therefore, in the study, we explored the impact of ER stress on EMT in RPE cells. 
      METHODS: Different concentrations of tunicamycin (TM) and thapsigargin (TG) were 
      used to induce ER stress in human RPE cells. The expression of epithelial marker, 
      mesenchymal markers and some of genes/proteins involved in TGF-beta/Smad signaling 
      were analized by qPCR, western blot or immunostaining at the condition with or 
      without stimulation of TGF-beta2 (10 ng/mL). Boyden chamber and scratch assay were 
      used to evaluate the migration of RPE cells, while cell viability and apoptosis 
      of RPE cells were measured by MTT and TUNEL assay, respectively. RESULTS: 
      Treatment of RPE cells with TM and TG (24 h) reduced the expression of alpha -SMA and 
      FN, and increased the expression of Occludin in a dose dependent manner at 
      protein level, which was highly associated with the expression of GRP78. 
      Treatment with TGF-beta2 significantly increased the expression of alpha-SMA and FN, and 
      decreased the expression of Occludin both in protein and mRNA levels, which was 
      significantly inhibited by a 4h pre-treatment with TM. In addition, the 
      expression of TGF-betaRII and Smad2/3, and mRNAs of TGF-betaRII and Smad3 were also 
      decreased by the TM treatment. TM-induced ER stress inhibited RPE cell migration, 
      and high concentrations of TM and TG reduced cell viability and induced apoptosis 
      of RPE cells. CONCLUSIONS: Chemical induction of ER stress inhibited EMT and 
      migration in RPE cells, possibly by inactivation of TGF-beta signaling, suggesting 
      that regulation of ER stress in RPE cells may be a new approach to prevent the 
      development of intraocular fibrosis.
CI  - (c) 2022 The Author(s). Published by IMR Press.
FAU - Ouyang, Sha
AU  - Ouyang S
AD  - Department of Ophthalmology, The Third Xiangya Hospital, Central South 
      University, 410000 Changsha, Hunan, China.
AD  - Eye Center of Xiangya Hospital, Central South University, 410008 Changsha, Hunan, 
      China.
AD  - Hunan Key Laboratory of Ophthalmology, 410008 Changsha, Hunan, China.
AD  - Department of Pathology, USC Roski Eye Institute, Keck School of Medicine of the 
      University of Southern California, Los Angeles, CA 90033, USA.
FAU - Ji, Dan
AU  - Ji D
AD  - Eye Center of Xiangya Hospital, Central South University, 410008 Changsha, Hunan, 
      China.
AD  - Hunan Key Laboratory of Ophthalmology, 410008 Changsha, Hunan, China.
FAU - He, Shikun
AU  - He S
AD  - Department of Pathology, USC Roski Eye Institute, Keck School of Medicine of the 
      University of Southern California, Los Angeles, CA 90033, USA.
FAU - Xia, Xiaobo
AU  - Xia X
AD  - Eye Center of Xiangya Hospital, Central South University, 410008 Changsha, Hunan, 
      China.
AD  - Hunan Key Laboratory of Ophthalmology, 410008 Changsha, Hunan, China.
LA  - eng
PT  - Journal Article
PL  - Singapore
TA  - Front Biosci (Landmark Ed)
JT  - Frontiers in bioscience (Landmark edition)
JID - 101612996
RN  - 0 (Retinal Pigments)
SB  - IM
MH  - *Cell Transdifferentiation
MH  - Endoplasmic Reticulum Stress
MH  - Epithelial Cells/metabolism
MH  - *Epithelial-Mesenchymal Transition/physiology
MH  - Humans
MH  - Retinal Pigment Epithelium/metabolism/pathology
MH  - Retinal Pigments/metabolism
OTO - NOTNLM
OT  - Cell movements
OT  - Endoplasmic reticulum stress
OT  - Epithelial-mesenchymal transition
OT  - Retinal pigment epithelial cells
OT  - TGF-beta signaling
COIS- The authors declare no conflict of interest. SH is serving as one of the Guest 
      Editor of this journal. We declare that SH had no involvement in the peer review 
      of this article and has no access to information regarding its peer review. Full 
      responsibility for the editorial process for this article was delegated to GP.
EDAT- 2022/03/01 06:00
MHDA- 2022/04/02 06:00
CRDT- 2022/02/28 21:02
PHST- 2021/08/31 00:00 [received]
PHST- 2021/12/07 00:00 [revised]
PHST- 2021/12/12 00:00 [accepted]
PHST- 2022/02/28 21:02 [entrez]
PHST- 2022/03/01 06:00 [pubmed]
PHST- 2022/04/02 06:00 [medline]
AID - S2768-6701(22)00376-8 [pii]
AID - 10.31083/j.fbl2702038 [doi]
PST - ppublish
SO  - Front Biosci (Landmark Ed). 2022 Jan 24;27(2):38. doi: 10.31083/j.fbl2702038.