In:
Current Pharmaceutical Design, Bentham Science Publishers Ltd., Vol. 28, No. 17 ( 2022-05), p. 1433-1443
Abstract:
Impaired wound healing is one of the most noteworthy features and troublesome complications
of diabetes mellitus, which arouses a rising global health concern without potent remedies. Thrombin is the major hemostatic agent applied at wound healing initiation and recently gained therapeutic credits in later
phases. However, a rare investigation achieved prolonged use of thrombin and probed the detailed mechanism. Objective: The objective of this study is to investigate the effects and mechanism of thrombin on diabetic skin
wound healing. Methods: The effect of thrombin on fibroblast proliferation, α-SMA, and Collagen I expression was firstly
studied in vitro by Cell Counting Kit 8 (CCK8) and western blotting. Then, the specific phosphorylation site of SMAD2/3 and their ERK1/2 dependence during thrombin treatment were assessed by western blotting for
mechanism exploration. After that, full-thickness wound defects were established in diabetic male SD rats and treated with thrombin in the presence or absence of PD98059 to observe the in vivo effects of thrombin and to
confirm its ERK dependence. Results: We found that thrombin promoted fibroblast proliferation and their α-SMA and Collagen I production.
Mechanistically, thrombin induced phosphorylation of Smad2 linker region (Ser245/250/255) through ERK1/2 phosphorylation but promoted phosphorylation of Smad3 linker region (Ser204) independent of ERK1/2. Histological
results showed that thrombin facilitated wound healing by promoting α-SMA and Collagen I expression, which was not abolished by inhibiting ERK phosphorylation. Conclusion: Collectively, this study validated the therapeutic efficacy of thrombin on diabetic wound healing
and identified both ERK-dependent and -independent Smad2/3 linker region phosphorylation as the essential signaling events in this process.
Type of Medium:
Online Resource
ISSN:
1381-6128
DOI:
10.2174/1381612828666220511125237
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2022
SSG:
15,3
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