Inhibition of collagen synthesis by IWR-1 in normal and keloid-derived skin fibroblasts
| Autor: | Tae-Jin Yoon, Jeung-Hoon Lee, Jin-Hyup Lee, Ming Ji Zhu, Ri-Hua Jiang, Wei-Tian Yin, Chang Deok Kim, Ming-Wei Zhou |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Male Pathology medicine.medical_specialty Matrix metalloproteinase Imides General Biochemistry Genetics and Molecular Biology Collagen receptor Extracellular matrix 03 medical and health sciences 0302 clinical medicine Keloid medicine Gelatinase Humans Collagenases General Pharmacology Toxicology and Pharmaceutics Wnt Signaling Pathway Cells Cultured Aged Skin Chemistry Wnt signaling pathway General Medicine Fibroblasts Middle Aged medicine.disease 030104 developmental biology 030220 oncology & carcinogenesis Enzyme Induction Cancer research Collagenase Quinolines Female Collagen Type I collagen medicine.drug |
| Zdroj: | Life sciences. 173 |
| ISSN: | 1879-0631 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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