Microarray analysis identifies matrix metalloproteinases (MMPs) as key genes whose expression is upregulated in human adipocytes by macrophage-conditioned medium

Paul Trayhurn

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

White adipose tissue exhibits inflammation as tissue mass expands in obesity, involving macrophage infiltration and a direct inflammatory response by adipocytes. DNA microarrays and conditioned medium have been used to examine the effects of macrophages on global gene expression in human adipocytes. SGBS adipocytes, differentiated in culture, were treated with macrophage-conditioned medium (U937 cells) for 4 or 24 h; control cells received unconditioned medium. Agilent arrays comprising 44,000 probes were used to analyse gene expression. Microarray analysis identified 1,088 genes differentially expressed in response to the conditioned medium at both 4 and 24 h (754 up-regulated, 334 down-regulated at 24 h); these included genes associated with inflammation and macrophage infiltration. A cluster of matrix metalloproteinase genes were highly up-regulated at both time-points, including MMP1, MMP3, MMP9, MMP10, MMP12 and MMP19. At 4 and 24 h, MMP1 was the most highly up-regulated gene (>2,400-fold increase in mRNA at 24 h). ELISA measurements indicated that substantial quantities of MMP1 and MMP3 were released from adipocytes incubated with conditioned medium, with little release by control adipocytes. Treatment with TNF¿ induced substantial increases in MMP1 (>100-fold) and MMP3 (27-fold) mRNA level and MMP1 and MMP3 release in adipocytes, suggesting that this cytokine could contribute to the stimulation of MMP expression by macrophages. In conclusion, macrophage-secreted factors induce a major inflammatory response in human adipocytes, with expression of MMP family members being strongly up-regulated. The induction of MMP1 and other MMPs suggests that macrophages stimulate tissue remodelling during adipose tissue expansion in obesity.
Original languageEnglish
Pages (from-to)1103-1114
Number of pages11
JournalPflügers Archiv European Journal of Physiology
Volume458
Issue number6
DOIs
Publication statusPublished - Oct 2009

Fingerprint Dive into the research topics of 'Microarray analysis identifies matrix metalloproteinases (MMPs) as key genes whose expression is upregulated in human adipocytes by macrophage-conditioned medium'. Together they form a unique fingerprint.

  • Cite this