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Inhibition of collagen synthesis by IWR-1 in normal and keloid-derived skin fibroblasts. | LitMetric

Inhibition of collagen synthesis by IWR-1 in normal and keloid-derived skin fibroblasts.

Life Sci

Department of Dermatology and Institute of Health Sciences, School of Medicine, Gyeongsang National University & Hospital, Jinju, Republic of Korea. Electronic address:

Published: March 2017

AI Article Synopsis

  • Keloids are benign tumors caused by an overgrowth of fibroblasts and collagen, with Wnt/β-catenin signaling playing a role in their development.
  • This study examines the small molecule inhibitor IWR-1, testing its effects on collagen and matrix metalloproteinase (MMP) production in both normal and keloid fibroblasts.
  • Results show IWR-1 reduces fibroblast proliferation and collagen secretion while increasing MMP expression and activity, suggesting its potential for treating keloid and other fibrotic skin diseases.*

Article 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.

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Source
http://dx.doi.org/10.1016/j.lfs.2016.12.003DOI Listing

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