Cargando…
Matrix metalloproteinase 12 modulates high-fat-diet induced glomerular fibrogenesis and inflammation in a mouse model of obesity
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 regulat...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4731752/ https://www.ncbi.nlm.nih.gov/pubmed/26822129 http://dx.doi.org/10.1038/srep20171 |
_version_ | 1782412583454638080 |
---|---|
author | Niu, Honglin Li, Ying Li, Haibin Chi, Yanqing Zhuang, Minghui Zhang, Tao Liu, Maodong Nie, Lei |
author_facet | Niu, Honglin Li, Ying Li, Haibin Chi, Yanqing Zhuang, Minghui Zhang, Tao Liu, Maodong Nie, Lei |
author_sort | Niu, Honglin |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4731752 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47317522016-02-03 Matrix metalloproteinase 12 modulates high-fat-diet induced glomerular fibrogenesis and inflammation in a mouse model of obesity Niu, Honglin Li, Ying Li, Haibin Chi, Yanqing Zhuang, Minghui Zhang, Tao Liu, Maodong Nie, Lei Sci Rep Article 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. Nature Publishing Group 2016-01-29 /pmc/articles/PMC4731752/ /pubmed/26822129 http://dx.doi.org/10.1038/srep20171 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Niu, Honglin Li, Ying Li, Haibin Chi, Yanqing Zhuang, Minghui Zhang, Tao Liu, Maodong Nie, Lei Matrix metalloproteinase 12 modulates high-fat-diet induced glomerular fibrogenesis and inflammation in a mouse model of obesity |
title | Matrix metalloproteinase 12 modulates high-fat-diet induced glomerular fibrogenesis and inflammation in a mouse model of obesity |
title_full | Matrix metalloproteinase 12 modulates high-fat-diet induced glomerular fibrogenesis and inflammation in a mouse model of obesity |
title_fullStr | Matrix metalloproteinase 12 modulates high-fat-diet induced glomerular fibrogenesis and inflammation in a mouse model of obesity |
title_full_unstemmed | Matrix metalloproteinase 12 modulates high-fat-diet induced glomerular fibrogenesis and inflammation in a mouse model of obesity |
title_short | Matrix metalloproteinase 12 modulates high-fat-diet induced glomerular fibrogenesis and inflammation in a mouse model of obesity |
title_sort | matrix metalloproteinase 12 modulates high-fat-diet induced glomerular fibrogenesis and inflammation in a mouse model of obesity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4731752/ https://www.ncbi.nlm.nih.gov/pubmed/26822129 http://dx.doi.org/10.1038/srep20171 |
work_keys_str_mv | AT niuhonglin matrixmetalloproteinase12modulateshighfatdietinducedglomerularfibrogenesisandinflammationinamousemodelofobesity AT liying matrixmetalloproteinase12modulateshighfatdietinducedglomerularfibrogenesisandinflammationinamousemodelofobesity AT lihaibin matrixmetalloproteinase12modulateshighfatdietinducedglomerularfibrogenesisandinflammationinamousemodelofobesity AT chiyanqing matrixmetalloproteinase12modulateshighfatdietinducedglomerularfibrogenesisandinflammationinamousemodelofobesity AT zhuangminghui matrixmetalloproteinase12modulateshighfatdietinducedglomerularfibrogenesisandinflammationinamousemodelofobesity AT zhangtao matrixmetalloproteinase12modulateshighfatdietinducedglomerularfibrogenesisandinflammationinamousemodelofobesity AT liumaodong matrixmetalloproteinase12modulateshighfatdietinducedglomerularfibrogenesisandinflammationinamousemodelofobesity AT nielei matrixmetalloproteinase12modulateshighfatdietinducedglomerularfibrogenesisandinflammationinamousemodelofobesity |