Microarray analysis identifies matrix metalloproteinases (MMPs) as key genes whose expression is up-regulated in human adipocytes by macrophage-conditioned medium
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 TNFalpha 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.
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Several ECM components are upregulated during fat mass expansion in states of obesity.
“We and others have demonstrated that several ECM components are upregulated during fat mass expansion in states of obesity (102, 103)”
From Adipose tissue remodeling and obesity (2011) · cites this paper as [103]
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- Authors
- O’Hara, A., Lim, F.-L., Mazzatti, D. J., & Trayhurn, P.
- Affiliations
- Unilever (United Kingdom) (GB)
- University of Liverpool (GB)
- Corresponding author
- Trayhurn, Paul
- Venue
- Pflügers Archiv - European Journal of Physiology
- Published
- 2009-07-09
- Volume
- 458
- Issue
- 6
- Pages
- 1103-1114
- ISSN
- 0031-6768 (ISSN-L)
- 1432-2013
- OpenAlex
- W2080442929
- Cited by
- 108
- References
- 53
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 2 · 2023: 5 · 2022: 6 · 2021: 5 · 2020: 6 · 2019: 2 · 2018: 5 · 2017: 5 · 2016: 9 · 2015: 8 · 2014: 6 · 2013: 8 · 2012: 16
- FWCI
- 7.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Pflügers Archiv - European Journal of Physiology (publishedVersion)
- PubMed (publishedVersion)
- CLOK (University of Central Lancashire) (submittedVersion)
- Funders
- Biotechnology and Biological Sciences Research Council
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- matrix metalloproteinases, adipocytes, macrophage-conditioned medium, obesity, adipose tissue inflammation, macrophage infiltration, MMP-1, MMP-3, MMP-9, MMP-12, MMP-10, MMP-19, TNF-α, gene expression, tissue remodeling, SGBS cells
- MeSH terms
- Humans, Inflammation, Macrophages, Tumor Necrosis Factor-alpha, Up-Regulation, Culture Media, Conditioned, Adipocytes, Matrix Metalloproteinase 3, U937 Cells, Oligonucleotide Array Sequence Analysis, Matrix Metalloproteinase 1, Matrix Metalloproteinases
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