Matrix metalloproteinase 12 modulates high-fat-diet induced glomerular fibrogenesis and inflammation in a mouse model of obesity.

Abstract

Obesity-induced kidney injury contributes to albuminuria, which is characterized by a progressive decline in renal function leading to glomerulosclerosis and renal fibrosis. Matrix metalloproteinases (MMPs) modulate inflammation and fibrosis by degrading a variety of extracellular matrix and regulating the activities of effector proteins. Abnormal regulation of MMP-12 expression has been implicated in abdominal aortic aneurysm, atherosclerosis, and emphysema, but the underlying mechanisms remain unclear. The present study examined the function of MMP-12 in glomerular fibrogenesis and inflammation using apo E(-/-) or apo E(-/-)MMP-12(-/-) mice and maintained on a high-fat-diet (HFD) for 3, 6, or 9 months. MMP-12 deletion reduced glomerular matrix accumulation, and downregulated the expression of NADPH oxidase 4 and the subunit-p67(phox), indicating the inhibition of renal oxidative stress. In addition, the expression of the inflammation-associated molecule MCP-1 and macrophage marker-CD11b was decreased in glomeruli of apo E(-/-)MMP-12(-/-) mice fed HFD. MMP-12 produced by macrophages infiltrating into glomeruli contributed to the degradation of collagen type IV and fibronectin. Crescent formation due to renal oxidative stress in Bowman's space was a major factor in the development of fibrogenesis and inflammation. These results suggest that regulating MMP-12 activity could be a therapeutic strategy for the treatment of crescentic glomerulonephritis and fibrogenesis.

• Authors: Honglin Niu, Ying Li, Haibin Li, Yanqing Chi, Minghui Zhuang, Tao Zhang, Maodong Liu, Lei Nie
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 20171 (Jan 29 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 26822129 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dietary Fats
• Matrix Metalloproteinase 12
• matrix metallopeptidase 12, mouse

Topics

• Animals
• Dietary Fats (adverse effects, pharmacology)
• Disease Models, Animal
• Fibrosis
• Glomerulosclerosis, Focal Segmental (chemically induced, enzymology, genetics, pathology)
• Kidney Glomerulus (enzymology, pathology)
• Macrophages (enzymology, pathology)
• Matrix Metalloproteinase 12 (biosynthesis, genetics)
• Mice
• Mice, Knockout
• Obesity (chemically induced, enzymology, genetics, pathology)