Roles of humoral factors and organ-organ or cell-cell communications in the development and progression of metabolic kidney diseases

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461226
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kumamoto University
• Principal Investigator: MUKOYAMA Masashi 熊本大学, 大学院生命科学研究部(医), 教授 (40270558)
• Co-Investigator(Renkei-kenkyūsha): MORI Kiyoshi 静岡県立大学, 薬学部, 特任教授 (60343232)
• Research Collaborator: KUWABARA Takashige 熊本大学, 大学院生命科学研究部, 助教 (00393356)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 腎臓学 / 内分泌学 / メタボリック症候群 / 糖尿病性腎症 / レニン・アンジオテンシン系 / ナトリウム利尿ペプチド / N型カルシウムチャネル / 自然炎症

Outline of Final Research Achievements

Lifestyle-related noncommunicable diseases such as diabetes, obesity and hypertension are the major risk for metabolic kidney diseases, in which endocrine dysregulation in organ-organ or cell-cell communications in the kidney may be suggested. We investigated roles of humoral factors in this pathophysiology.
We found that the natriuretic peptide (ANP and BNP) receptor GC-A in podocytes is important in protecting against aldosterone-induced glomerular injury in mice. We also found the role of N-type calcium channels in sympathetic nerve activation and podocyte injury in obese diabetic mice with nephropathy. Finally, we found the pathogenic role of local homeostatic inflammation driven by toll-like receptor 4 and its endogenous ligand myeloid-related protein 8 (MRP8), a macrophage-derived proinflammatory factor, in mouse models of diabetes-hyperlipidemia as well as proliferative nephritis. These findings may provide potential therapeutic strategies for metabolic kidney diseases.

Free Research Field

内科系臨床医学・腎臓内科学