首页> 外文期刊>Matrix biology: Journal of the International Society for Matrix Biology >Lysophosphatidic acid inhibits TGF-beta-mediated stimulation of type I collagen mRNA stability via an ERK-dependent pathway in dermal fibroblasts.
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Lysophosphatidic acid inhibits TGF-beta-mediated stimulation of type I collagen mRNA stability via an ERK-dependent pathway in dermal fibroblasts.

机译:溶血磷脂酸通过皮肤成纤维细胞中的ERK依赖性途径抑制TGF-β介导的I型胶原mRNA稳定性的刺激。

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摘要

Lysophosphatidic acid (LPA) is a serum-derived pleiotropic mediator with a potential role in wound repair. Since extracellular matrix (ECM) deposition is a critical part of wound healing, this study was designed to examine whether LPA is involved in ECM regulation. Using human dermal fibroblasts, we demonstrate that LPA counteracts transforming growth factor-beta (TGF-beta) stimulation of type I collagen mRNA and protein. This factor elicits its inhibitory effects at the posttranscriptional level via destabilization of type I collagen mRNA. Furthermore, using the mitogen-activated protein kinase kinase (MEK) inhibitor PD98059, we show that the extracellular signal-regulated kinase (ERK) pathway is a negative regulator of the TGF-beta-induced stabilization of type I collagen mRNA, and that the activation of the ERK pathway by LPA mediates their inhibitory effects on collagen production. In conclusion, this study describes a novel function for LPA as an antagonist of TGF-beta induced ECM deposition. These findings may be relevant to physiologic wound repair and may be useful in designing therapeutic agents to prevent excessive scarring.
机译:溶血磷脂酸(LPA)是一种源自血清的多效介体,在伤口修复中具有潜在作用。由于细胞外基质(ECM)沉积是伤口愈合的关键部分,因此本研究旨在检查LPA是否参与ECM调节。使用人类皮肤成纤维细胞,我们证明LPA抵消I型胶原mRNA和蛋白质的转化生长因子-β(TGF-β)刺激。该因子通过I型胶原mRNA的去稳定作用,在转录后水平上引发其抑制作用。此外,使用有丝分裂原激活的蛋白激酶激酶(MEK)抑制剂PD98059,我们发现细胞外信号调节激酶(ERK)通路是TGF-β诱导的I型胶原mRNA稳定化的负调节剂,并且LPA对ERK途径的激活介导了它们对胶原蛋白产生的抑制作用。总之,这项研究描述了LPA作为TGF-β诱导的ECM沉积拮抗剂的新功能。这些发现可能与生理性伤口修复有关,并且在设计治疗剂以防止过度瘢痕形成方面可能有用。

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