TIMP-1 promotes age-related renal fibrosis through upregulating ICAM-1 in human TIMP-1 transgenic mice.
Imbalance of matrix metalloproteinases and tissue inhibitors of metalloproteinases (MMPs/TIMPs) takes part in age-related renal fibrosis; so does molecular inflammation. As several inflammatory mediators including intercellular adhesion molecule-1 (ICAM-1) are substrates of MMPs, we speculated that TIMP-1 might affect ICAM-1 through MMPs and subsequently promote age-related renal fibrosis. Then, we observed changes of kidney in human TIMP-1 transgenic mice and wild-type mice of different ages. It was found that the expressions and activities of gelatinases were downregulated; the expressions of ICAM-1, collagen III, collagen IV, and transforming growth factor (TGF)-beta1 were upregulated; and the number of infiltrating macrophages was increased in kidneys of 24-month-old TIMP-1 transgenic mice with high expressions of TIMP-1, compared with wild-type mice. Our results indicated that TIMP-1 could promote age-related renal fibrosis, which was partly attributed to enhancing inflammation through upregulation of ICAM-1.
Zhang
Xueguang
X
Department of Nephrology, Kidney Center and Key Lab of PLA, Chinese General Hospital of PLA, Fuxing Road 28, Beijing 100853, PR China.
Chen
Xiangmei
X
Hong
Quan
Q
Lin
Hongli
H
Zhu
Hanyu
H
Liu
Qingxin
Q
Wang
Jianzhong
J
Xie
Yuansheng
Y
Shang
Xiyao
X
Shi
Suozhu
S
Lu
Yang
Y
Yin
Zhong
Z
D000375:Aging / Q000502:physiology*; D000419:Albuminuria; D000818:Animals; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D015536:Down-Regulation / Q000502:physiology; D005355:Fibrosis; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D012333:RNA, Messenger / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology*
D024061:Collagen Type III; D024141:Collagen Type IV; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D018799:Intercellular Adhesion Molecule-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D003404:Creatinine; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9