The development of therapeutic strategies for chronic kidney disease targeting the transcription factor OASIS in podocytes

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15027
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: Osaka University
• Principal Investigator: Obana Masanori 大阪大学, 薬学研究科, 准教授 (50745883)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ポドサイト / 慢性腎臓病 / 転写因子

Outline of Final Research Achievements

Although there is an unmet medical need in the treatment of kidney diseases, the pathological mechanisms of kidney diseases remain to be elucidated. Previously, we found that OASIS is expressed in podocytes of murine kidneys. Therefore, in the present study, we examined the pathological roles of OASIS in podocytes. OASIS was increased in cultured podocytes and murine glomeruli by LPS treatment. Moreover, LPS- or diabetes-induced kidney dysfunction was reduced in podocyte-specific OASIS knockout mice. Surprisingly, podocyte-specific OASIS transgenic mice showed severe albuminuria, accompanied by increased podocyte/tubular injury and tubulointerstitial fibrosis. Taken together, the upregulation of OASIS in podocytes contributes to disruption of kidney homeostasis.

Free Research Field

分子腎臓病学

Academic Significance and Societal Importance of the Research Achievements

腎疾患、特に慢性腎臓病は新たな国民病として注目され、透析導入や心血管病のリスクファクターであるため、その予防や治療が重要である。腎臓病の予防法や治療法を確立する上で、腎臓病の成り立ちを理解することは重要だが、未だ腎疾患病態形成機構には不明な点が多い。本研究では、腎構成細胞のポドサイトにおける転写因子OASISが、腎疾患病態形成に関わることを見出した。本研究成果は、新たな腎臓病治療法の開発に繋がるものと期待される。