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Inhibition of Collagen Synthesis by IWR-1 in Normal and Keloid-Derived Skin Fibroblasts

Ming-Wei Zhou, Wei-Tian Yin, Ri-Hua Jiang, Jin-Hyup Lee, Chang-Deok Kim, Jeung-Hoon Lee, Ming Ji Zhu, Tae-Jin Yoon

Life Sci. 2017 Mar 15;173:86-93.

PMID: 27939785

Abstract:

Aims:
Keloid is a benign tumor that is characterized by the hyperproliferation of dermal fibroblasts and excessive deposition of extracellular matrix (ECM) especially the collagen. Aberrant activation of Wnt/β-catenin signaling is implicated in the pathogenesis of keloid. In this study, we investigated the effects of IWR-1, a small molecule inhibitor for Wnt/β-catenin signaling via the inhibition of tankyrase, on production of collagen and matrix metalloproteinase (MMP) in dermal fibroblasts.
Main methods:
We cultured human normal skin- and keloid-derived fibroblasts, then treated with IWR-1. The effects of IWR-1 on collagen and MMP production were determined by Western blot, ELISA and zymography.
Key findings:
IWR-1 significantly suppressed the proliferation and migration of both the normal and keloid fibroblasts. IWR-1 also inhibited the production and secretion of type I collagen from the fibroblasts. In addition, IWR-1 significantly increased the expression of MMPs, such as MMP-1, MMP-3 and MMP-13, along with the increase of gelatinase activity. These results suggest that inhibitory effect of IWR-1 on collagen production may be related with the increased MMP activity.
Significance:
This study provides the possible action mechanism of IWR-1 on regulation of collagen expression, on which to base further investigation for preventing skin fibrotic diseases such as keloid.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR4243595 IWR-1 IWR-1 Price
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