@§Í±ü´¾³Ì¼ÈãðèßéAa«tÇðMªÆ·é¶KµaÖAtÇimetabolic kidney diseasejðSÉA
ÌQiWÉÍAÇÇÆµÄtoll-like receptor 4iTLR4jVOiâ»Ìàö«Khmyeloid-related protein 8iMRP8jAyÑ±êðU±·éÇöqªdvÈððÊ½·Êª¾çêÄ¢éBAMRP8ÍÇaÏð½fÅ«ésqÈwWÌÂ\«ª èAVK}[J[ÆµÄÌpðÚwµ½¢ðsÁÄ¢éBÜ½AAaf}EXÌP£
AtÉ¨¯é_î½t²ßAÁÉA_r²ß@Ìð¾ÉæègñÅ¢éBWA×ÇÔÝ×EÉ¨¯éAjArðîµ½_rÌªqîÕð¾ç©É·éÆÆàÉA_r\ªáºµ½ÛÌtgDà_¯ipHáºjªtáQÉ^¦ée¿ð¢µÄ¢éBÜ½AA×Ç×EÉ»·éZ§³]ÊöqNFAT5inuclear factor of activated T cells 5jÌðÉÂ¢Ä¢µÄ¢éBA×ÇÁÙINFAT5¹}EXðp¢Ä»Ì¶IÓ`ð¾ç©ÉµA}«táQâ«táQiWÉ¨¯éNFAT5Ìðð¾yÑnò^[QbgÆµÄÌÂ\«ÉÂ¢Ä¢µÄ¢éB
1. Metabolic kidney disease including diabetic nephropathy and nephrosclerosis is the leading cause of end-stage renal disease. We aim to clarify the mechanisms and pathophysiology of glomerular diseases, and to explore novel diagnostic and therapeutic strategies to combat metabolic kidney disease. We have already shown that toll-like receptor 4 (TLR4) and its endogenous ligand myeloid-related protein 8 (MRP8), together with paracrine factors activating them, contribute to the progression of glomerulopathy as local proinflammatory mediators. As a sensitive biomarker to indicate local inflammation in the kidney, we are currently developing a novel measurement technique to determine urinary MRP8. In addition, we are investigating the effects of novel compounds ameliorating ER stress and energy expenditure upon renal diseases based on the glomerular microarray analysis in diabetic mouse models.
2. Molecular mechanisms for acid-base homeostasis in the kidney have been investigated. We are studying molecular basis and regulatory mechanisms for acid secretion by the intercalated cells of the renal collecting duct, together with the pathophysiology of impaired acid secretion in kidney disease progression. In addition, the role of nuclear factor of activated T cells 5 (NFAT5), an osmoprotective transcription factor, in the kidney has been investigated. Using inducible conditional knockout mice, the pathophysiological roles of NFAT5 in normal and diseased kidney have been studied.
3. In order to explore the molecular mechanisms for renal sodium handling and the pathogenesis of hypertension, the regulation of the epithelial sodium channel (ENaC) and the roles of serine proteases as activators of ENaC have been investigated. Furthermore, the specific serine proteases participating in the development of renal injury in salt-sensitive hypertension and metabolic syndrome models have been searched using the proteomics technique, and the role of serine proteases in the pathogenesis of such conditions has been examined. In addition, we are exploring a novel therapeutic strategy targeting serine proteases for the treatment of hypertension and related renal disorders.