Work

Targeting Itga8 Mitigates Neurogenic Bladder Fibrosis Driven by Trem2⁺ Macrophage‐Derived Fn1 via FAK/RhoA/ROCK Signaling

Year: 2025

Type: article

Abstract: Neurogenic bladder (NB)‐induced fibrosis is the major cause of irreversible bladder dysfunction, yet the underlying mechanisms remain undefined. Here, leveraging single‐cell RNA sequencing, the fibrotic landscape of NB is delineated and a distinct integrin α8 (Itga8) ⁺ fibroblast population. The Itga8⁺ fibroblasts expand substantially during the acute phase post‐injury and exhibit a fibrogenic transcriptional profile. Mechanistically, Itga8 is found to coordinate cytoskeletal remodeling via the FAK/RhoA/ROCK signaling to facilitate fibroblast activation. Moreover, fibroblast activation is orchestrated by Trem2⁺ macrophages, which secrete Fn1 to engage Itga8 on fibroblasts, thereby reinforcing the pro‐fibrotic communication between fibroblasts and macrophages. Notably, macrophage depletion markedly attenuates fibrosis and restores bladder function, underscoring their pivotal role in NB pathogenesis. In vivo, conditional deletion of Itga8 ( Col1a2 ‐CreERT; Itga8 fl/fl ) or local knockdown of Itga8 significantly attenuates collagen deposition and improves voiding efficiency. Collectively, this study reveals a novel Itga8‐centered fibroinflammatory axis and nominates Itga8 as a promising therapeutic target for delaying fibrosis progression and restoring bladder function.

Source: Advanced Science

DOI: 10.1002/advs.202510631