Journal
JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION
Volume 111, Issue 11, Pages 589-598Publisher
ELSEVIER TAIWAN
DOI: 10.1016/j.jfma.2012.09.008
Keywords
endothelial cell; macrophage; myofibroblast; pericyte; renal fibrosis
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Funding
- National Science Council [99-2628-B-002-013, 101-2321-B-002-060, 101-2314-B-002-084, 101-2314-B-002-149]
- National Taiwan University Hospital [99-S1302]
- Mrs. Hsiu-Chin Lee Kidney Research Foundation
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Renal fibrosis is a disease affecting millions worldwide and is a harbinger of progressive renal failure. Understanding the mechanisms of renal fibrosis is important for discovering new therapies that are required to prevent loss of renal function. Recently, we identified pericytes that line the kidney microvasculature as the precursor cells of the scar-producing myofibroblasts during kidney injury. Kidney pericytes are extensively branched cells embedded within the capillary basement membrane and stabilize the capillary network through tissue inhibitor of metalloproteinase 3 and angiogenic growth factors. Pericytes detach from endothelial cells and migrate into the interstitial space where they undergo a transition into myofibroblasts after injury. Activation of endothelium, pericyte-myofibroblast transition, and recruitment of inflammatory macrophages lead to capillary rarefaction and fibrosis. Targeting endothelium-pericyte crosstalk by inhibiting vascular endothelial cell growth factor receptors and platelet-derived growth factor receptors in response to injury have been identified as new therapeutic interventions. Furthermore, targeting macrophage activation has also been proven as a novel and safe therapeutic approach for pericyte-myofibroblast transition. However, we are still far from understanding the interaction between pericytes and other cellular elements in normal physiology and during kidney fibrosis. Further studies will be required to translate into more specific therapeutic approaches. Copyright (c) 2012, Elsevier Taiwan LLC & Formosan Medical Association. All rights reserved.
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