Article ; Online: The small GTPase regulatory protein Rac1 drives podocyte injury independent of cationic channel protein TRPC5.
2023 Volume 103, Issue 6, Page(s) 1056–1062
Abstract: Transient receptor potential canonical channels (TRPCs) are non-selective cationic channels that play a role in signal transduction, especially in G -protein-mediated signaling cascades. TRPC5 is expressed predominantly in the brain but also in the ... ...
| Abstract | Transient receptor potential canonical channels (TRPCs) are non-selective cationic channels that play a role in signal transduction, especially in G -protein-mediated signaling cascades. TRPC5 is expressed predominantly in the brain but also in the kidney. However, its role in kidney physiology and pathophysiology is controversial. Some studies have suggested that TRPC5 drives podocyte injury and proteinuria, particularly after small GTPase Rac1 activation to induce the trafficking of TRPC5 to the plasma membrane. Other studies using TRPC5 gain-of-function transgenic mice have questioned the pathogenic role of TRPC5 in podocytes. Here, we show that TRPC5 over-expression or inhibition does not ameliorate proteinuria induced by the expression of constitutively active Rac1 in podocytes. Additionally, single-cell patch-clamp studies did not detect functional TRPC5 channels in primary cultures of podocytes. Thus, we conclude that TRPC5 plays a role redundant to that of TRPC6 in podocytes and is unlikely to be a useful therapeutic target for podocytopathies. |
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| MeSH term(s) | Mice ; Animals ; Podocytes/pathology ; TRPC Cation Channels/genetics ; TRPC Cation Channels/metabolism ; Glomerulosclerosis, Focal Segmental/pathology ; Monomeric GTP-Binding Proteins/metabolism ; TRPC6 Cation Channel/genetics ; TRPC6 Cation Channel/metabolism ; Proteinuria/pathology ; Mice, Transgenic ; Transcription Factors/metabolism | |||||
| Chemical Substances | TRPC Cation Channels ; Monomeric GTP-Binding Proteins (EC 3.6.5.2) ; TRPC6 Cation Channel ; Transcription Factors ; Trpc5 protein, mouse | |||||
| Language | English | |||||
| Publishing date | 2023-02-05 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural | |||||
| ZDB-ID | 120573-0 | |||||
| ISSN | 1523-1755 ; 0085-2538 | |||||
| ISSN (online) | 1523-1755 | |||||
| ISSN | 0085-2538 | |||||
| DOI | 10.1016/j.kint.2023.01.016 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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