慢性腎臓病に伴う尿細管障害及び間質線維化のバイオマーカーの同定  [in Japanese] Identification of Biomarkers for Tubular Injury and Interstitial Fibrosis in Chronic Kidney Disease  [in Japanese]

Access this Article

Author(s)

Abstract

 In chronic kidney disease (CKD), progressive nephron loss causes tubulointerstitial fibrosis and progressive tubular injury. Recent identification of the major cell populations of myofibroblast precursors in the kidney has enabled us to dissect the fibrogenic process after tubular injury. Kidney pericytes are a possible precursor of myofibroblasts, and may be promising targets for treating fibrogenesis. Our recent studies have shown that pericytes activate Toll-like receptor (TLR) 2/4- and myeloid differentiation primary response 88 (MyD88)-dependent proinflammatory signaling in response to renal tubular injury. We also found active roles of inflammasomes in kidney pericytes, leading to interleukin (IL)-1β and IL-18 secretion. Genetic ablation of MyD88 in pericytes, or pharmacological inhibition of MyD88 signaling by an IL-1 receptor-associated kinase 4 (IRAK4) inhibitor, halted interstitial fibrosis after renal tubular injury. Our data indicate that pericytes not only contribute to interstitial fibrosis by aberrant wound-healing responses, but also serve as innate immune surveillance cells that regulate the inflammatory process, exacerbating tubular injury by the release of cytokines and chemokines. On the other hand, our recent study using a microarray analysis aimed to identify molecular changes that reflected the histopathological progression of renal tubulointerstitial fibrosis and tubular cell damage in patients with CKD. The results indicated that 5 genes were up-regulated in the kidney of CKD patients, and that their expression levels correlated with the extent of tubulointerstitial fibrosis and tubular cell injury. These findings provide important information for the development of diagnostic tools and therapeutic agents for predicting and preventing progressive renal disease.<br>

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 137(11), 1355-1360, 2017

    The Pharmaceutical Society of Japan

Codes

  • NII Article ID (NAID)
    130006191261
  • NII NACSIS-CAT ID (NCID)
    AN00284903
  • Text Lang
    JPN
  • ISSN
    0031-6903
  • NDL Article ID
    028622348
  • NDL Call No.
    Z19-411
  • Data Source
    NDL  J-STAGE 
Page Top