PMID- 32926102
OWN - NLM
STAT- MEDLINE
DCOM- 20210331
LR  - 20211204
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 61
IP  - 11
DP  - 2020 Sep 1
TI  - S100A4 Silencing Facilitates Corneal Wound Healing After Alkali Burns by 
      Promoting Autophagy via Blocking the PI3K/Akt/mTOR Signaling Pathway.
PG  - 19
LID - 10.1167/iovs.61.11.19 [doi]
LID - 19
AB  - PURPOSE: This study investigated the role of S100 calcium binding protein A4 
      (S100A4) in corneal wound healing and the underlying mechanism of the 
      S100A4-mediated PI3K/Akt/mammalian target of rapamycin (mTOR) pathway. METHODS: 
      The rabbit corneal alkali burn model was established in vivo. S100A4 expression, 
      wound healing, inflammation, and autophagy in rabbit cornea after alkali burn 
      were detected. The NaOH-treated rabbit corneal stromal cells (rCSCs) were 
      transfected with overexpressed S100A4 or silencing S100A4 to examine the effect 
      of S100A4 on corneal wound healing in vitro. The effect of S100A4 on cell 
      viability, proliferation, migration, invasion, fibrosis, and autophagy of rCSCs 
      after alkali burn was analyzed. Then the functional rescue experiments were 
      carried out. The PI3K inhibitor, LY294002, was used to elucidate the 
      PI3K/Akt/mTOR signaling pathway in rCSCs. RESULTS: S100A4 silencing promoted 
      rabbit corneal wound healing by inhibiting fibrosis and inflammation and 
      promoting autophagy in alkali-burned cornea, corresponding to increased levels of 
      LC3, Beclin 1, and Atg4B but lowered alpha-smooth muscle actin, TNF-a, and p62 
      levels. Moreover, silencing S100A4 inhibited proliferation, migration, invasion, 
      and fibrosis of NaOH-treated rCSCs and promoted the differentiation of rCSCs into 
      corneal cells and the autophagy of damaged rCSCs. The inhibitory role of S100A4 
      in wound healing was achieved via activation of the PI3K/Akt/mTOR pathway. 
      CONCLUSIONS: S100A4 silencing confers a promising effect on wound healing of 
      alkali-burned cornea by blocking the PI3K/Akt/mTOR pathway, supporting the 
      advancement of corneal gene therapies for wound healing.
FAU - Wang, Yulin
AU  - Wang Y
AD  - Department of Ophthalmology, First Affiliated Hospital of Nanchang University, 
      Nanchang, P.R. China.
FAU - Gao, Guiping
AU  - Gao G
AD  - Department of Ophthalmology, First Affiliated Hospital of Nanchang University, 
      Nanchang, P.R. China.
FAU - Wu, Ying
AU  - Wu Y
AD  - Department of Otolaryngology, First Affiliated Hospital of Nanchang University, 
      Nanchang, P.R. China.
FAU - Wang, Yuqin
AU  - Wang Y
AD  - State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital 
      of Wenzhou Medical University, Wenzhou, P.R. China.
FAU - Wu, Xiaorong
AU  - Wu X
AD  - Department of Ophthalmology, First Affiliated Hospital of Nanchang University, 
      Nanchang, P.R. China.
FAU - Zhou, Qiong
AU  - Zhou Q
AD  - Department of Ophthalmology, First Affiliated Hospital of Nanchang University, 
      Nanchang, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Alkalies)
RN  - 0 (S100 Calcium-Binding Protein A4)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
EIN - Invest Ophthalmol Vis Sci. 2021 Mar 1;62(3):19. PMID: 33720275
MH  - Alkalies/toxicity
MH  - Animals
MH  - Autophagy
MH  - Burns, Chemical/*genetics/metabolism/pathology
MH  - Corneal Injuries/chemically induced/*genetics/metabolism
MH  - Disease Models, Animal
MH  - Eye Burns/*genetics/metabolism/pathology
MH  - Female
MH  - *Gene Expression Regulation
MH  - Male
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Rabbits
MH  - S100 Calcium-Binding Protein A4/biosynthesis/*genetics
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Wound Healing/genetics
PMC - PMC7490227
COIS- Disclosure: Y. Wang, None; G. Gao, None; Y. Wu, None; Y. Wang, None; X. Wu, None; 
      Q. Zhou, None
EDAT- 2020/09/15 06:00
MHDA- 2021/04/01 06:00
PMCR- 2020/09/14
CRDT- 2020/09/14 15:46
PHST- 2020/09/14 15:46 [entrez]
PHST- 2020/09/15 06:00 [pubmed]
PHST- 2021/04/01 06:00 [medline]
PHST- 2020/09/14 00:00 [pmc-release]
AID - 2770790 [pii]
AID - IOVS-19-28833 [pii]
AID - 10.1167/iovs.61.11.19 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2020 Sep 1;61(11):19. doi: 10.1167/iovs.61.11.19.