Integrin α8-Mediated Pericyte Morphogenesis Controls Blood-Brain Barrier Integrity.

Abstract

Pericytes exhibits distinct morphological features on microvessels during various stages of brain-blood barrier (BBB) development and neurological disorders. However, the underlying mechanisms by which pericyte morphology influences BBB integrity are not yet fully understood. Integrin α8 (ITGA8) is prominently expressed in mature pericytes, which tightly associate with endothelial cells during BBB maturation and post-ischemic vascular remodeling. ITGA8-deficient mice shows the disrupted pericyte morphology, including shortened processes and reduced vascular coverage, leads to compromised BBB integrity. Mechanistically, ITGA8 regulates pericyte morphology via the Rho-ROCK signaling, subsequently impacting BBB function through TGF-β1 activation, which underscores its role in cytoskeletal organization and microvascular stability. In an ischemic stroke model, ITGA8 deficiency results in increased BBB permeability, reduced pericyte coverage, and worsened neurological recovery. Conversely, adeno-associated virus (AAV)-mediated ITGA8 overexpression restores pericyte morphology and improveS post-stroke neurological outcomes. ITGA8 is identified as a key regulator of pericyte morphology and function, which are essential for maintaining BBB integrity, thereby highlighting the therapeutic potential of targeting ITGA8 for BBB repair and neurovascular recovery.