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Effects of Transforming Growth Factor-β1 (TGF-β1) Signaling Pathway on Cell Proliferation and Cell Migration Are Mediated by Ubiquitin Specific Protease 4 (USP4) in Hypertrophic Scar Tissue and Primary Fibroblast Cultures

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eMediNexus    06 June 2020

Hypertrophic scars result from an abnormal repair response to trauma in the skin and involves fibroblasts proliferation with increased collagen deposition. Transforming growth factor-ß1 (TGF-ß1) and TGF-ß receptor type I (TGF-ßR1) are involved in tissue repair and are increased by ubiquitin-specific protease 4 (USP4).

A new study published in Medical Science Monitor investigated the effects of TGF-ßR1 and USP4 in human tissue samples of hypertrophic scar and on cell proliferation and cell migration in primary fibroblast cultures, in vitro.

In this study, skin excision tissue samples with adjacent normal skin were obtained from 15 patients with hypertrophic scar – which provided tissue sections and primary fibroblast culture for analysis. Immunohistochemistry detected the expression of USP4 and TGF-ßR1 in tissue sections. Fibroblast proliferation, apoptosis and migration were measured by the Cell Counting Kit-8 (CCK-8) assay, flow cytometry and a wound-healing assay, respectively.

It was observed that the expression of USP4 and TGF-ßR1 in hypertrophic scars were increased compared to the normal skin. Fibroblasts cultured from hypertrophic scar tissue showed increased expression of USP4 and TGF-ßR1. On the other hand, fibroblast transfection with USP4 short-interfering RNA (siRNA) resulted in reduced fibroblast proliferation and migration and increased apoptosis. Downregulation of USP4 inhibited the expression of TGF-ßR1 protein and increased the expression levels of Smad7 protein.

The results indicated that USP4 regulated the proliferation, migration and apoptosis of hypertrophic scar fibroblasts by regulating the TGF-ß1 signaling pathway.

Source: Medical Science Monitor. 2020 Apr 20;26:e920736. doi: 10.12659/MSM.920736.

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