Novel cell-to-cell communications between macrophages and fibroblasts regulate obesity-induced adipose tissue fibrosis.

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Tác giả: Satoko Arakawa, Atsushi Enomoto, Kenji Ikeda, Ayaka Ito, Hiro Kohda, Tadasuke Komori, Kouji Matsushima, Yuki Miyai, Yoshihiro Morikawa, Kozue Ochi, Yoshihiro Ogawa, Atsuhito Saiki, Shigeyuki Shichino, Shigeomi Shimizu, Takayoshi Suganami, Takehiko Takeda, Miyako Tanaka, Ichiro Tatsuno, Satoshi Ueha, Eri Wada, Xunmei Yuan

Ngôn ngữ: eng

Ký hiệu phân loại: 573.1636 *Circulatory system

Thông tin xuất bản: United States : Diabetes , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 684632

Recent evidence has shown that adipose tissue eventually develops fibrosis through complex cellular crosstalk. Although advances in single-cell transcriptomics have provided new insights into cell diversity during this process, little is known about the interactions among the distinct cell types. In this study, we employed single-cell analytical approaches to investigate cell-tocell communications between macrophages and fibroblasts in the adipose tissue of diet-induced obese mice. Spatial transcriptomics was used to understand local cellular interaction within crown-like structures (CLSs), a characteristic histological feature of adipose tissue in obesity driving inflammation and fibrosis. Macrophages and fibroblasts were divided into several subclusters that appeared to interact more intensely and complexly with the degree of obesity. Besides previously reported Lipid-associated macrophages (LAMs), we found a small subcluster expressing Macrophage-inducible C-type lectin (Mincle), specifically localizing to CLSs. Mincle signaling increased the expression of Oncostatin M (Osm), suppressing collagen gene expression in adipose tissue fibroblasts. Consistent with these findings, Osm-deficiency in immune cells enhanced obesity-induced adipose tissue fibrosis in vivo. Moreover, Osm expression was positively correlated with Mincle expression in human adipose tissue during obesity. Our results suggest that Osm secreted by Mincle-expressing macrophages is involved in dynamic adipose tissue remodeling in the proximity of CLSs.
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