Periostin is induced by IL-4/IL-13 in dermal fibroblasts and promotes RhoA/ROCK pathway-mediated TGF-β1 secretion in abnormal scar formation
Periostin is induced by IL-4/IL-13 in dermal fibroblasts and promotes RhoA/ROCK pathway-mediated TGF-β1 secretion in abnormal scar formation
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DOI：
10.1080/2000656x.2019.1612752
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发表时间：
2019-05-07
影响因子：
1.2
通讯作者：
Hosokawa, Ko
中科院分区：
文献类型：
--
作者：
Maeda, Daisuke;Kubo, Tateki;Hosokawa, Ko
皮肤损伤后可出现过多瘢痕形成，导致瘢痕形成异常，如瘢痕疙瘩和增生性瘢痕，其特征是真皮内细胞外基质大量沉积。骨膜蛋白是一种细胞外基质蛋白，在皮肤发育和维持体内平衡中起着至关重要的作用，也参与皮肤疾病，如全身性/局限性硬皮病、伤口闭合和异常疤痕形成。然而，骨膜蛋白参与异常瘢痕形成的机制尚不完全清楚。在这项研究中，我们研究了骨膜蛋白参与异常疤痕形成的机制。IL-4和IL-13是Th2型免疫反应的细胞因子，在异常疤痕中被上调。用IL-4和IL-13处理人真皮成纤维细胞（HDFs），显著提高了骨膜蛋白mRNA和蛋白的水平，并促进了HDFs的骨膜蛋白分泌。转化生长因子- β 1 （tgf - β 1）对HDFs的作用与IL-4和IL-13相同。用骨膜蛋白刺激HDFs可促进RhoA/ROCK途径介导的HDFs分泌tgf - β 1。我们的研究结果表明，IL-4和IL-13诱导骨膜蛋白的表达和分泌，而分泌的骨膜蛋白又诱导RhoA/ROCK途径介导的tgf - β 1分泌。然后，分泌的tgf - β 1进一步诱导骨膜素的产生和分泌，从而促进异常疤痕的形成。
Excess scar formation can occur after skin injury and lead to abnormal scar formation, such as keloids and hypertrophic scars, which are characterised by substantial deposition of extracellular matrix in the dermis. Periostin, an extracellular matrix protein that plays a crucial role in skin development and maintaining homeostasis, is also involved in skin disorders such as systemic/limited scleroderma, wound closure, and abnormal scar formation. However, the mechanism of periostin involvement in abnormal scar formation is not yet fully understood. In this study, we investigated the mechanism by which periostin is involved in abnormal scar formation. Treatment of human dermal fibroblasts (HDFs) with IL-4 and IL-13, which are cytokines of Th2 type immune responses that are up-regulated in abnormal scars, dramatically elevated the levels of periostin mRNA and protein, and also promoted the secretion of periostin by HDFs. Transforming growth factor-beta 1 (TGF-beta 1) had the same effect on HDFs as IL-4 and IL-13. Stimulation of HDFs with periostin promoted RhoA/ROCK pathway-mediated TGF-beta 1 secretion from HDFs. Our results suggest that IL-4 and IL-13 induce periostin expression and secretion, and in turn, secreted periostin induces RhoA/ROCK pathway-mediated TGF-beta 1 secretion. Secreted TGF-beta 1 then induces further periostin production and secretion, thereby promoting abnormal scar formation.