The IκB kinase inhibitor ACHP strongly attenuates TGFβ1-induced myofibroblast formation and collagen synthesis

Journal of Cellular and Molecular Medicine
Masum M Mia, Ruud A Bank

Abstract

Excessive accumulation of a collagen-rich extracellular matrix (ECM) by myofibroblasts is a characteristic feature of fibrosis, a pathological state leading to serious organ dysfunction. Transforming growth factor beta1 (TGFβ1) is a strong inducer of myofibroblast formation and subsequent collagen production. Currently, there are no remedies for the treatment of fibrosis. Activation of the nuclear factor kappa B (NF-κB) pathway by phosphorylating IκB with the enzyme IκB kinase (IKK) plays a major role in the induction of fibrosis. ACHP {2-Amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-(4-piperidinyl)-3 pyridinecarbonitrile}, a selective inhibitor of IKK, prohibits the activation of the NF-κB pathway. It is not known whether ACHP has potential anti-fibrotic properties. Using adult human dermal and lung fibroblasts we have investigated whether ACHP has the ability to inhibit the TGFβ1-induced transition of fibroblasts into myofibroblasts and its excessive synthesis of ECM. The presence of ACHP strongly suppressed the induction of the myofibroblast markers alpha-smooth muscle actin (αSMA) and SM22α, as well as the deposition of the ECM components collagen type I and fibronectin. Furthermore, post-treatment with ACHP partly rev...Continue Reading

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Citations

Jul 5, 2017·Journal of the American Heart Association·Florence L JohnsonChristoph Thiemermann
Jul 24, 2018·Oncotarget·Atrayee BhattacharyaArchana Dhasarathy
Oct 27, 2016·Journal of Cellular and Molecular Medicine·Lin ShiXiangdong Wang
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Jun 15, 2021·Frontiers in Medicine·Li ZhangJun Mao
Mar 31, 2021·American Journal of Respiratory and Critical Care Medicine·Konstantin TsoyiIvan O Rosas

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Methods Mentioned

BETA
nuclear translocation
transfection
antisense oligonucleotides
PCR
fluorescence imaging microscopy
SMA

Software Mentioned

Graph
TissueQuest
GraphPad
‐ Pad Prism

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