Departments
Integrated Medical and Pharmaceutical Sciences
Nephrology
- Division
- Integrated Medical and Pharmaceutical Sciences
- Great Departments
- Basic and Clinical Medicine
Staff
| Professor | YOKOI Hideki |
|---|---|
| Associate Professor | KUWABARA Takashige ktakasea(at mark)kumamoto-u.ac.jp |
| Assistant Professor | MIZUMOTO Teruhiko tmizumoto(at mark)kumamoto-u.ac.jp |
| Assistant Professor | FUJIMOTO Daisuke dfleppard1002(at mark)kumamoto-u.ac.jp |
Research theme
- 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. In hemodialysis patients, MRP8 appears to be associated with prognosis and we are investigating the pathological significance of MRP8. Furthermore, we have successfully established a high-quality single-cell database on diabetic mouse glomeruli, and identified candidate molecules involved in glucose metabolism, inflammation, and the cytoskeleton. Currently, we are conducting functional analysis for novel therapeutic applications.
- The role of nuclear factor of activated T-cells 5 (NFAT5), an osmoprotective transcription factor, in the kidney has been investigated. GWAS has shown that the NFAT5 variants are associated with hypertension. We have shown that the renal tubular cell-specific NFAT5 knockout mice exhibited insufficient urine concentration and salt-sensitive hypertension. The involvement of NFAT5 in chronic kidney disease is under investigation. In addition, 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 renal collecting duct, together with the pathophysiology of impaired acid secretion in kidney disease progression.
- 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.