Effects of the platelet CLEC-2 on podocytes of injured glomeruli

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K17257
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Okayama University (2021-2023); Tokai University (2020)
• Principal Investigator: Tanaka Keiko 岡山大学, 医歯薬学域, 助教 (80794370)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: ポドサイト / 血小板 / CLEC-2 / Podoplanin

Outline of Final Research Achievements

Podoplanin (PDPN) is strongly expressed on podocyte cell membranes; the endogenous ligand for PDPN is CLEC-2 expressing on platelets. Podocytes are normally sequestered from CLEC-2, but when glomerular barrier is injured, podocytes gain access to CLEC-2. We tested the effect of CLEC-2 on podocytes in vitro and in vivo. Cultured podocytes treated with Fc-CLEC-2 showed that CLEC-2 induced dephosphorylation of ERM proteins. Treated podocytes also showed dissociation of F-actin filaments from PDPN, F-actin degradation, detachment, and round morphology. Normal mouse kidneys were perfused with FLAG-CLEC-2. CLEC-2 induced dephosphorylation of ERM and widening of foot processes of podocytes. Platelets were detected by immunostaining for CD41 in the urine of mice with podocyte injury. These findings suggest that when platelets leak from injured glomeruli, platelet-derived CLEC-2 may act on PDPNs on podocytes, causing morphological changes and detachment, further exacerbating podocyte injury.

Free Research Field

腎臓病学

Academic Significance and Societal Importance of the Research Achievements

本研究は、古くから知られていたポドサイトタンパク質Podoplaninの知られざる新たな機能を解明し、ポドサイトが糸球体濾過バリア破綻を伝えるCLEC-2のセンサーを備えているという事を明らかにした。このことは今後ポドサイト保全の新しい治療ターゲットにつながる可能性がある。また今まで顧みられなかった尿中血小板に、蛋白尿や血尿とは異なる新たな診断的価値を与える可能性がある。