PDF(Pubmed)
Abstract：
Pathological fibrosis is a significant complication of surgical procedures resulting from the accumulation of excess collagen at the site of repair which can compromise the tissue architecture and severely impede the function of the affected tissue. Few prophylactic treatments exist to counteract this process; however, the use of amniotic membrane allografts has demonstrated promising clinical outcomes. This study aimed to identify the underlying mechanism of action by utilizing relevant models that accurately represent the pathophysiology of the disease state. This study employed a pro-fibrotic in vitro system using TGFβ1 stimulation and macromolecular crowding techniques to evaluate the mechanism by which amniotic membrane allografts regulate collagen biosynthesis and deposition. Following treatment with dehydrated human amnion chorion membrane (DHACM), subsequent RNA sequencing and functional enrichment with Reactome pathway analysis indicated that amniotic membranes are indeed capable of regulating genes associated with the composition and function of the extracellular matrix. Furthermore, macromolecular crowding was used in vitro to expand the evaluation to include both the effects of DHACM and a lyophilized human amnion/chorion membrane (LHACM). DHACM and LHACM regulate the TGFβ pathway and myofibroblast differentiation. Additionally, both DHACM and LHACM modulate the production, secretion, and deposition of collagen type I, a primary target for pathological fibrosis. These observations support the hypothesis that amniotic membranes may interrupt pathological fibrosis by regulating collagen biosynthesis and associated pathways.
摘要：
病理性纤维化是外科手术的重要并发症,这是由于在修复部位积累了过量的胶原,这可能损害组织结构并严重阻碍受影响组织的功能。很少有预防性治疗来抵消这一过程；然而，羊膜同种异体移植物的使用显示了有希望的临床结果.这项研究旨在通过利用准确代表疾病状态病理生理学的相关模型来确定潜在的作用机制。这项研究采用了使用TGFβ1刺激和大分子拥挤技术的体外促纤维化系统，以评估羊膜同种异体移植物调节胶原蛋白生物合成和沉积的机制。用脱水的人羊膜绒毛膜（DHACM）处理后，随后的RNA测序和Reactome途径分析的功能富集表明羊膜确实能够调节与细胞外基质的组成和功能相关的基因。此外，在体外使用大分子拥挤来扩展评估，以包括DHACM和冻干的人羊膜/绒毛膜（LHACM）的作用。DHACM和LHACM调节TGFβ途径和肌成纤维细胞分化。此外,DHACM和LHACM都可以调节产量，分泌，和I型胶原蛋白的沉积，病理性纤维化的主要目标。这些观察结果支持羊膜可能通过调节胶原生物合成和相关途径来中断病理性纤维化的假设。
