Medical College of Wisconsin
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Brain vascular stability relies on PAK2-cilia-PDGF-BB-HSPGs on basolateral side of endothelium. Life Sci Alliance 2026 Mar;9(3)

Date

01/06/2026

Pubmed ID

41490797

Pubmed Central ID

PMC12769094

DOI

10.26508/lsa.202503460

Scopus ID

2-s2.0-105026638885 (requires institutional sign-in at Scopus site)   3 Citations

Abstract

Endothelial cells (ECs) in the brain communicate with mural cells to facilitate vascular stability. Platelet-derived growth factor-BB (PDGF-BB)/platelet-derived growth factor receptor-β (PDGFR-β) signaling mechanism at EC-mural cell interface helps stabilize the vasculature. How this paracrine signaling is mediated is not known. Our laboratory studies endothelial cilia, a microtubule-based organelle, and its role in promoting vascular stability. We discovered that brain endothelial cilia are located primarily on the basolateral side, and PDGF-BB is expressed in EC cilium. Thus, we hypothesized that endothelium cilium in conjunction with PDGF-BB on the basolateral side is responsible for mural cell recruitment. In this study, using a combination of zebrafish, mice, and human brain model systems, we have established a signaling paradigm wherein p21-activated kinase (PAK2) and ADP-ribosylation factor-13b (ARL13b) in ECs induce secretion of PDGF-BB. PDGF-BB associates with heparan sulfate proteoglycans (HSPGs) to form a gradient around ECs. Disrupting PAK2 affects ciliogenesis, HSPGs, and PDGF-BB gradient. We unravel a new mechanism involving endothelial cilia/PAK2-mediated PDGF-BB secretion, and retention by periendothelial HSPGs to promote vascular stability via recruiting mural cells.

Author List

Prabhudesai S, Thirugnanam K, Song X, Yang H, Errede M, Girolamo F, Neumann T, Marzullo A, Bafti S, Vanderhoef K, Rarick KR, Spearman AD, Pan AY, Alvarez CA, Yang J, Zhang F, Dordick JS, Virgintino D, Wang L, Ramchandran R

Authors

Amy Y. Pan PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin
Andrew Spearman MD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Karthikeyan Thirugnanam Research Scientist I in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Brain
Cilia
Endothelial Cells
Endothelium, Vascular
Humans
Mice
Signal Transduction
Zebrafish
p21-Activated Kinases