Angiotensin‐converting enzyme inhibitor works as a scar formation inhibitor by down‐regulating Smad and TGF‐β‐activated kinase 1 (TAK1) pathways in mice

Abstract

ACEI showed anti-fibrotic properties in scar formation by mediating downstream peptides to suppress TGF-β1/Smad and TGF-β1/TAK1 pathways. These findings suggest that dual inhibition of Smad and TAK1 signalling by ACEI is a useful strategy for the development of new anti-fibrotic agents.

Potential effect of non-thermal plasma for the inhibition of scar formation: a preliminary report

“…As an upper reaching signal molecule, TGF-β regulates the expression of multiple downstream signaling molecules involved in scar formation via both canonical and noncanonical pathways 25 . The TGF-β1/Smad2/3 pathway is considered as one of the most important signaling pathways in scar formation because it supports the overproduction of ECM components and the over-proliferation of fibroblasts, which was confirmed in our previous study 26,27 . Thus, down-regulating the expression of the TGF-β1/Smad2/3 pathway is a promising strategy in scar management.…”

Angiotensin‐converting enzyme inhibitor and angiotensin II type 1 receptor blocker: Potential agents to reduce post‐surgical scar formation in humans

“…0 (0-0) 0 (0-0) 0 (0-0) 0 (0-0) 1 by reducing fibroblast proliferation and decreasing collagen deposition through the smad and TGF-beta-activated kinase 1 (TAK1) pathways. 5 We also confirmed these results in mouse NIH 3T3 fibroblasts and rats with acute dermal wounds. 6 The anti-scar effect of ACEI/ARB has been well demonstrated in animal experiments, so we hope to further study its effect in humans.…”

“…This is supported by the results of our previous animal experiments, especially that both internal and external application ACEI/ARBs can improve scars in rodents. 5,6 However, there are some limitation to this study. Firstly, the sample size of the study was relatively small and most of them were women.…”

“…4 It has been proved that ACEI and ARB could inhibit scar formation by down-regulating transforming growth factor-β1 (TGF-β1) in animal models. 5,6 Clinical applications of ACEI and ARB drugs for the treatment of fibrotic diseases of other organs have been reported, for example, the anti-fibrotic effect of Ang II blocking agents has been proven in hepatitis C patients with liver fibrosis, 7 but the relationship between ACEI/ARB and normal scar formation after surgery in humans has not been established. ACEIs and ARBs are widely used antihypertensive drugs with relatively low toxicity 8 ; if they can be applied to prevent or treat scarring, they will become a good choice of clinical medication for scar management.…”

The role of the renin‐angiotensin system in skin physiology and pathophysiology

“…[14,15,25] Regarding the role of AT 1 Rs during the remodelling phase, it is well documented that AT 1 R stimulation acts pro-fibrotic by increasing levels of TGFβ, which in turn initiates canonical TGFβ signalling including phosphorylation of Smad2/3 and enhanced transcription of connective tissue growth factor (CTGF/CCN2) and also non-canonical TGFβ signalling including MAP kinase activation. [35,37,38] These signalling pathways result in stimulation of ECM synthesis by fibroblasts and in transition from fibroblasts into myofibroblast, which have contractile properties and are essential for wound contraction. [35,38] Regarding the role of AT 2 Rs in the later phases of wound healing, based on data about AT 2 R-mediated anti-inflammatory and anti-fibrotic actions obtained from a multitude of mainly non-dermatological preclinical disease models, [10,11] it can be assumed that AT 2 Rs are involved in dampening the inflammatory response and-most of all-in balancing the formation of granulation and scar tissue.…”