https://scholars.lib.ntu.edu.tw/handle/123456789/540352
標題: | Pericyte TIMP3 and ADAMTS1 modulate vascular stability after kidney injury | 作者: | Schrimpf C. Xin C. Campanholle G. Gill S.E. Stallcup W. SHUEI-LIONG LIN Davis G.E. Gharib S.A. Humphreys B.D. Duffield J.S. |
公開日期: | 2012 | 卷: | 23 | 期: | 5 | 起(迄)頁: | 868-883 | 來源出版物: | Journal of the American Society of Nephrology | 摘要: | Kidney pericytes are progenitors of scar-forming interstitial myofibroblasts that appear after injury. The function of kidney pericytes as microvascular cells and how these cells detach from peritubular capillaries and migrate to the interstitial space, however, are poorly understood. Here, we used an unbiased approach to identify genes in kidney pericytes relevant to detachment and differentiation in response to injury in vivo, with a particular focus on genes regulating proteolytic activity and angiogenesis. Kidney pericytes rapidly activated expression of a disintegrin and metalloprotease with thrombospondin motifs-1 (ADAMTS1) and downregulated its inhibitor, tissue inhibitor ofmetalloproteinase 3 (TIMP3) in response to injury. Similarly to brain pericytes, kidney pericytes bound to and stabilized capillary tube networks in three-dimensional gels and inhibited metalloproteolytic activity and angiogenic signaling in endothelial cells. In contrast, myofibroblasts did not have these vascular stabilizing functions despite their derivation from kidney pericytes. Pericyte-derived TIMP3 stabilized and ADAMTS1 destabilized the capillary tubular networks. Furthermore,mice deficient in Timp3 had a spontaneousmicrovascular phenotype in the kidney resulting from overactivated pericytes and were more susceptible to injury-stimulated microvascular rarefaction with an exuberant fibrotic response. Taken together, these data support functions for kidney pericytes inmicrovascular stability, highlight central roles for regulators of extracellular proteolytic activity in capillary homoeostasis, and identify ADAMTS1 as a marker of activation of kidney pericytes. Copyright ? 2012 by the American Society of Nephrology. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84860645452&doi=10.1681%2fASN.2011080851&partnerID=40&md5=57bd9f65e1773687a5e672ecf20d5eb3 https://scholars.lib.ntu.edu.tw/handle/123456789/540352 |
ISSN: | 1046-6673 | DOI: | 10.1681/ASN.2011080851 | SDG/關鍵字: | 5' nucleotidase; ADAMTS1 protein; ADAMTS2 protein; ADAMTS3 protein; aggrecanase 1; aggrecanase 2; alpha smooth muscle actin; angiopoietin 1; angiopoietin 2; CD31 antigen; collagen type 1; creatinine; gelatinase A; gelatinase B; Hermes antigen; kallikrein; matrilysin; matrix metalloproteinase; matrix metalloproteinase 14; matrix metalloproteinase 23; metalloproteinase; platelet derived growth factor beta receptor; stromelysin 3; synaptopodin; Thy 1 antigen; tissue inhibitor of metalloproteinase 1; tissue inhibitor of metalloproteinase 3; unclassified drug; WT1 protein; angiogenesis; animal cell; animal experiment; animal model; animal tissue; apoptosis; article; blood vessel parameters; blood vessel stability; brain cell; capillary tube; cell adhesion; cell differentiation; cell maturation; cell migration; cell proliferation; controlled study; creatinine blood level; down regulation; endothelium cell; enzyme activity; gene expression; gene identification; homeostasis; human; human cell; human tissue; in vivo study; kidney cell; kidney fibrosis; kidney injury; microarray analysis; microvasculature; molecular stability; mouse; myofibroblast; nonhuman; pericyte; phenotype; priority journal; protein degradation; protein expression; protein phosphorylation; signal transduction; ADAM Proteins; Animals; Capillaries; Cell Adhesion; Cells, Cultured; Humans; Kidney; Kidney Diseases; Mice; Mice, Inbred C57BL; Mice, Transgenic; Myofibroblasts; Neovascularization, Physiologic; Oligonucleotide Array Sequence Analysis; Pericytes; Tissue Inhibitor of Metalloproteinase-3; Ureteral Obstruction; Vascular Endothelial Growth Factor A |
顯示於: | 醫學系 |
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