Abstract
Several studies have suggested that extracellular matrix (ECM) remodeling and the microenvironment are tightly associated with adipogenesis and adipose angiogenesis. In the present study, we demonstrated that transforming growth factor-beta induced (TGFBI) suppresses angiogenesis stimulated by adipocyte-conditioned medium (Ad-CM), both in vitro and in vivo. TGFBI knockout (KO) mice exhibited increased numbers of blood vessels in adipose tissue, and blood vessels from these mice showed enhanced infiltration into Matrigel containing Ad-CM. The treatment of Ad-CM-stimulated SVEC-10 endothelial cells with TGFBI protein reduced migration and tube-forming activity. TGFBI protein suppressed the activation of the Src and extracellular signaling-related kinase signaling pathways of these SVEC-10 endothelial cells. Our findings indicated that TGFBI inhibited adipose angiogenesis by suppressing the activation of Src and ERK signaling pathways, possibly because of the stimulation of the angiogenic activity of endothelial cells.
Highlights
Several studies have suggested that extracellular matrix (ECM) remodeling and the microenvironment are tightly associated with adipogenesis and adipose angiogenesis
We found that the deletion of transforming growth factor-beta induced (TGFBI) promoted the activation of Src and ERK in adipose tissue cells, while treatment of TGFBI protein inhibited the activation of these proteins in endothelial cells
The mRNA expression of TGFBI was detected in inguinal white adipose tissue from wild type (WT) mice (Supplementary Fig. 1a), the relative expression was lower than that of liver tissue, which has been reported to express TGFBI abundantly 22,23
Summary
Several studies have suggested that extracellular matrix (ECM) remodeling and the microenvironment are tightly associated with adipogenesis and adipose angiogenesis. Previous studies have suggested that remodeling of the ECM through the deletion of the collagen VI gene results in the expansion of adipose tissue without the development of inflammation, accompanied by suppression of the activation of the MAPK signaling pathway[8,9]. From this perspective, targeting angiogenesis through the alternation of the ECM expression is a potential therapeutic strategy for metabolic diseases, such as obesity, diabetes, and angiogenesis-associated diseases. TGFBI is present in human adipocytes, and the signaling pathway in which it participates could be involved in the differentiation of a dipocytes[21]
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