Angiotensin-converting enzyme inhibitor reduces scar formation by inhibiting both canonical and noncanonical TGF-β1 pathways

Scientific Reports
Qing-Qing FangWei-Qiang Tan

Abstract

Angiotensin-converting enzyme inhibitors (ACEIs) can improve the fibrotic processes in many internal organs. Recent studies have shown a relationship between ACEI with cutaneous scar formation, although it has not been confirmed, and the underlying mechanism is unclear. In this study, we cultured mouse NIH 3T3 fibroblasts with different concentrations of ACEI. We measured cell proliferation with a Cell Counting Kit-8 and collagen expression with a Sirius Red Collagen Detection Kit. Flow cytometry and western blotting were used to detect transforming growth factor β1 (TGF-β1) signaling. We also confirmed the potential antifibrotic activity of ACEI in a rat scar model. ACEI reduced fibroblast proliferation, suppressed collagen and TGF-β1 expression, and downregulated the phosphorylation of SMAD2/3 and TAK1, both in vitro and in vivo. A microscopic examination showed that rat scars treated with ramipril or losartan were not only narrower than in the controls, but also displayed enhanced re-epithelialization and neovascularization, and the formation of organized granulation tissue. These data indicate that ACEI inhibits scar formation by suppressing both TGF-β1/SMAD2/3 and TGF-β1/TAK1 pathways, and may have clinical utility in the ...Continue Reading

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Citations

Aug 14, 2018·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Keshvad HedayatyanfardHamideh Moravvej
Nov 23, 2019·Bioscience, Biotechnology, and Biochemistry·Satoshi SuzukiKen-Ichi Kimura
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Aug 7, 2019·Plastic and Reconstructive Surgery·Amanda MurphyMichael Bezuhly
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Jul 23, 2020·Experimental Dermatology·Igor Maciel Souza SilvaUlrike Muscha Steckelings
Dec 31, 2020·Pharmaceutics·Alma Akhmetova, Andrea Heinz
Jun 17, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Tao ZhangWei-Qiang Tan

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Methods Mentioned

BETA
fluorescence-activated cell sorting
FACS
transfection
electrophoresis
Infrared Imaging

Software Mentioned

FlowJo
Image Studio Lite
SPSS

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