SMAD公司
基因敲除
癌症研究
化学
小干扰RNA
细胞生物学
纤维化
转化生长因子
信号转导
MAPK/ERK通路
分子生物学
生物
转染
医学
内科学
细胞凋亡
生物化学
基因
作者
Hui Song Cui,So Young Joo,Yoon Soo Cho,June-Bum Kim,Cheong Hoon Seo
标识
DOI:10.1016/j.abb.2020.108322
摘要
Post-burn hypertrophic scar (HTS) is a form of excessive dermal fibrosis characterized by cutaneous scarring, which is common in patients following burn injury. Moreover, at least 50% of HTS are accompanied by inflammation. Cytoplasmic polyadenylation element binding (CPEB) proteins are key mRNA-binding proteins that control the translation of several mRNAs. However, their potential roles in treating dermal fibrosis and scarring remain unknown. Therefore, in this study, we aimed to investigate the effects of small interfering RNA (siRNA)-mediated knockdown of CPEB1 or CPEB4 in human THP-1 macrophages and dermal fibroblasts treated with LPS and TGF-β1. We found significantly increased CPEB1 and CPEB4 mRNA and protein levels in LPS-treated THP-1 cells and TGF-β1–treated fibroblasts. CPEB1 and CPEB4 knockdowns suppressed LPS-activated TAK1 signaling cascades by reducing the levels of TNF-α and phosphorylated TAK1, p38, ERK, JNK, and NF-κB-p65 in THP-1 cells. CPEB1 and CPEB4 knockdowns also attenuated TGF-β1-activated Smad-dependent and -independent signaling cascades by reducing the levels of TAK1, p38, ERK, JNK, and phosphorylated Smad 2 and Smad 1/5/8 in fibroblasts. Furthermore, CPEB1 or CPEB4 knockdown markedly decreased the levels of fibrosis markers, including α-SMA, type I collagen, and fibronectin in fibroblasts. Our findings indicate that CPEB1 and CPEB4 are involved in the regulation of the TAK1 and Smad signalings in human macrophages and dermal fibroblasts. These activities may play a role in cutaneous scarring responses.
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