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脂肪组织和脂肪分泌组在系统性硬化症中的作用。

Adipose tissue and adipose secretome in systemic sclerosis.

机构信息

Department of Rheumatology, University Medical Centre Ljubljana.

Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.

出版信息

Curr Opin Rheumatol. 2021 Nov 1;33(6):505-513. doi: 10.1097/BOR.0000000000000838.

Abstract

PURPOSE OF REVIEW

Adipose tissue is closely associated with systemic sclerosis (SSc)-pathology, both anatomically and functionally. This review focuses on local effects of adipocytes in the context of adipose to mesenchymal transdifferentiation (AMT), effects of the adipose stromal vascular fraction on SSc pathogenesis and systemic effects of adipose tissue secretome.

RECENT FINDINGS

Novel populations of fibroblasts evolving from adipose tissue were identified- for example COL11+ cancer-associated fibroblasts differentiated from adipose-derived stromal cells. Lipofibroblasts in human lungs were described using nonconventional markers that allow more effective population identification. These findings could make an important contribution to further clarification of adipocyte involvement in SSc.Recent studies confirmed that lipolysis contributes to fibrogenesis through AMT differentiation and release of fatty acids (FA). Unbalanced metabolism of FA has been reported in several studies in SSc. Other adipose tissue secretome molecules (e.g. lysophosphatidic acid), novel adipokines and extracellular vesicles from adipose mesenchymal stem cells make important contributions to the pro-/antifibrotic balance.

SUMMARY

There is a growing evidence of important contribution of adipose tissue and its secretome to SSc pathogenesis. Novel techniques such as single-cell RNA sequencing (scRNAseq) and metabolomics, albeit challenging to use in adipose tissue, will provide further evidence.

摘要

目的综述

脂肪组织与系统性硬化症(SSc)的病理学密切相关,在解剖学和功能上都是如此。本综述重点介绍脂肪细胞在脂肪间充质转分化(AMT)背景下的局部作用、脂肪基质血管部分对 SSc 发病机制的影响以及脂肪组织分泌组的全身作用。

最近的发现

已经确定了源自脂肪组织的新型成纤维细胞群体,例如从脂肪来源的基质细胞分化而来的 COL11+癌相关成纤维细胞。使用允许更有效群体鉴定的非传统标记物描述了人肺中的脂肪成纤维细胞。这些发现可能对进一步阐明脂肪细胞在 SSc 中的作用做出重要贡献。最近的研究证实,脂肪分解通过 AMT 分化和脂肪酸(FA)的释放促进纤维化。在 SSc 的几项研究中报道了 FA 的代谢失衡。脂肪间充质干细胞的其他脂肪组织分泌组分子(例如溶血磷脂酸)、新型脂肪因子和细胞外囊泡对促/抗纤维化平衡有重要贡献。

总结

越来越多的证据表明脂肪组织及其分泌组对 SSc 的发病机制有重要贡献。尽管在脂肪组织中使用单细胞 RNA 测序(scRNAseq)和代谢组学等新技术具有挑战性,但它们将提供更多证据。

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