PMID- 38546583
OWN - NLM
STAT- MEDLINE
DCOM- 20240329
LR  - 20240402
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 65
IP  - 3
DP  - 2024 Mar 5
TI  - Lack of Elevated Expression of TGFbeta3 Contributes to the Delay of Epithelial Wound 
      Healing in Diabetic Corneas.
PG  - 35
LID - 10.1167/iovs.65.3.35 [doi]
LID - 35
AB  - PURPOSE: To investigate the mechanisms underlying the differential roles of TGFbeta1 
      and TGFbeta3 in accelerating corneal epithelial wound healing (CEWH) in diabetic 
      (DM) corneas, with normoglycemia (NL) corneas as the control. METHODS: Two types 
      of diabetic mice, human corneal organ cultures, mouse corneal epithelial 
      progenitor cell lines, and bone marrow-derived macrophages (BMDMs) were employed 
      to assess the effects of TGFbeta1 and TGFbeta3 on CEWH, utilizing quantitative PCR, 
      western blotting, ELISA, and whole-mount confocal microscopy. RESULTS: Epithelial 
      debridement led to an increased expression of TGFbeta1 and TGFbeta3 in cultured human 
      NL corneas, but only TGFbeta1 in DM corneas. TGFbeta1 and TGFbeta3 inhibition was 
      significantly impeded, but exogenous TGFbeta1 and, more potently, TGFbeta3 promoted 
      CEWH in cultured TKE2 cells and in NL and DM C57BL6 mouse corneas. Wounding 
      induced similar levels of p-SMAD2/SMAD3 in NL and DM corneas but weaker ERK1/2, 
      Akt, and EGFR phosphorylation in DM corneas compared to NL corneas. Whereas TGFbeta1 
      augmented SMAD2/SMAD3 phosphorylation, TGFbeta3 preferentially activated ERK, PI3K, 
      and EGFR in healing DM corneas. Furthermore, TGFbeta1 and TGFbeta3 differentially 
      regulated the expression of S100a9, PAI-1, uPA/tPA, and CCL3 in healing NL and DM 
      corneas. Finally, TGFbeta1 induced the expression of M1 macrophage markers iNOS, 
      CD86, and CTGF, whereas TGFbeta3 promoted the expression of M2 markers CD206 and NGF 
      in BMDMs from db/db or db/+ mice. CONCLUSIONS: Hyperglycemia disrupts the 
      balanced expression of TGFbeta3/TGFbeta1, resulting in delayed CEWH, including impaired 
      sensory nerve regeneration in the cornea. Supplementing TGFbeta3 in DM wounds may 
      hold therapeutic potential for accelerating delayed wound healing in diabetic 
      patients.
FAU - Gao, Nan
AU  - Gao N
AD  - Departments of Ophthalmology and Anatomy and Cell Biology, Kresge Eye Institute, 
      Wayne State University School of Medicine, Detroit, Michigan, United States.
FAU - Yu, Fu-Shin
AU  - Yu FS
AD  - Departments of Ophthalmology and Anatomy and Cell Biology, Kresge Eye Institute, 
      Wayne State University School of Medicine, Detroit, Michigan, United States.
LA  - eng
GR  - R01 EY010869/EY/NEI NIH HHS/United States
GR  - R01 EY017960/EY/NEI NIH HHS/United States
GR  - R01 EY035785/EY/NEI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - 0 (TGFB3 protein, human)
RN  - 0 (Tgfb3 protein, mouse)
RN  - 0 (Transforming Growth Factor beta3)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - Cornea
MH  - *Corneal Injuries
MH  - *Diabetes Mellitus, Experimental
MH  - ErbB Receptors
MH  - *Hyperglycemia
MH  - Mice, Inbred C57BL
MH  - *Transforming Growth Factor beta3/genetics
PMC - PMC10981440
COIS- Disclosure: N. Gao, None; F.-S. Yu, None
EDAT- 2024/03/28 12:50
MHDA- 2024/03/29 06:46
PMCR- 2024/03/28
CRDT- 2024/03/28 11:33
PHST- 2024/03/29 06:46 [medline]
PHST- 2024/03/28 12:50 [pubmed]
PHST- 2024/03/28 11:33 [entrez]
PHST- 2024/03/28 00:00 [pmc-release]
AID - 2793488 [pii]
AID - IOVS-23-39230 [pii]
AID - 10.1167/iovs.65.3.35 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2024 Mar 5;65(3):35. doi: 10.1167/iovs.65.3.35.