We have located links that may give you full text access.
Journal Article
Research Support, Non-U.S. Gov't
ARHGEF7 ( β -PIX) Is Required for the Maintenance of Podocyte Architecture and Glomerular Function.
BACKGROUND: Previous studies showed that Cdc42, a member of the prototypical Rho family of small GTPases and a regulator of the actin cytoskeleton, is critical for the normal development and health of podocytes. However, upstream regulatory mechanisms for Cdc42 activity in podocytes are largely unknown.
METHODS: We used a proximity-based ligation assay, BioID, to identify guanine nucleotide exchange factors that activate Cdc42 in immortalized human podocytes. We generated podocyte-specific ARHGEF7 (commonly known as β -PIX) knockout mice by crossing β -PIX floxed mice with Podocin-Cre mice. Using shRNA, we established cultured mouse podocytes with β -PIX knockdown and their controls.
RESULTS: We identified β -PIX as a predominant guanine nucleotide exchange factor that interacts with Cdc42 in human podocytes. Podocyte-specific β -PIX knockout mice developed progressive proteinuria and kidney failure with global or segmental glomerulosclerosis in adulthood. Glomerular podocyte density gradually decreased in podocyte-specific β -PIX knockout mice, indicating podocyte loss. Compared with controls, glomeruli from podocyte-specific β -PIX knockout mice and cultured mouse podocytes with β -PIX knockdown exhibited significant reduction in Cdc42 activity. Loss of β -PIX promoted podocyte apoptosis, which was mediated by the reduced activity of the prosurvival transcriptional regulator Yes-associated protein.
CONCLUSIONS: These findings indicate that β -PIX is required for the maintenance of podocyte architecture and glomerular function via Cdc42 and its downstream Yes-associated protein activities. This appears to be the first evidence that a Rho-guanine nucleotide exchange factor plays a critical role in podocytes.
METHODS: We used a proximity-based ligation assay, BioID, to identify guanine nucleotide exchange factors that activate Cdc42 in immortalized human podocytes. We generated podocyte-specific ARHGEF7 (commonly known as β -PIX) knockout mice by crossing β -PIX floxed mice with Podocin-Cre mice. Using shRNA, we established cultured mouse podocytes with β -PIX knockdown and their controls.
RESULTS: We identified β -PIX as a predominant guanine nucleotide exchange factor that interacts with Cdc42 in human podocytes. Podocyte-specific β -PIX knockout mice developed progressive proteinuria and kidney failure with global or segmental glomerulosclerosis in adulthood. Glomerular podocyte density gradually decreased in podocyte-specific β -PIX knockout mice, indicating podocyte loss. Compared with controls, glomeruli from podocyte-specific β -PIX knockout mice and cultured mouse podocytes with β -PIX knockdown exhibited significant reduction in Cdc42 activity. Loss of β -PIX promoted podocyte apoptosis, which was mediated by the reduced activity of the prosurvival transcriptional regulator Yes-associated protein.
CONCLUSIONS: These findings indicate that β -PIX is required for the maintenance of podocyte architecture and glomerular function via Cdc42 and its downstream Yes-associated protein activities. This appears to be the first evidence that a Rho-guanine nucleotide exchange factor plays a critical role in podocytes.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app