Numb Mediates IL-1β/TGF-β1-Driven Inflammation-Fibrosis Coupling in Idiopathic Pulmonary Fibrosis.
TL;DR
Numb participates in coordinating inflammatory and fibrotic responses in IPF and may act as a regulatory mediator in inflammation - fibrosis coupling and may act as a regulatory mediator in inflammation - fibrosis coupling.
Abstract
Background
In idiopathic pulmonary fibrosis (IPF), inflammatory signaling and fibrotic remodeling often coexist, yet the mechanism linking these processes remains unclear. Numb, a cell fate determinant protein, has been implicated in tissue remodeling but its role in inflammation - fibrosis coupling is not well defined.
Methods
Public transcriptomic datasets were analyzed to assess NUMB expression patterns and associated pathways. A bleomycin (BLM)-induced mouse model was used for in vivo validation. In vitro, MRC-5 fibroblasts were stimulated with IL-1β and TGF-β1, alone or in combination, followed by Numb siRNA intervention. Cell viability, migration, cytokine secretion, and fibrosis-related protein expression were evaluated.
Results
Transcriptomic analysis showed a non-significant but consistent upward trend of NUMB in IPF tissues (p = .18), with pathway-level enrichment in inflammatory and extracellular matrix processes. In BLM-treated mice, IL-1β and TGF-β1 levels were significantly increased (both p < .001), accompanied by upregulation of Numb (p < .05), α-SMA, and Collagen I (both p < .001). In vitro, IL-1β and TGF-β1 synergistically enhanced cell viability and migration (both p < .001), as well as protein expression (p < .001). Numb silencing reduced cytokine secretion (p < .001), cell activation (p < .05-0.001), and fibrosis-related protein expression (p < .001).
Conclusion
Numb participates in coordinating inflammatory and fibrotic responses in IPF and may act as a regulatory mediator in inflammation - fibrosis coupling.