Neuronal β-III Tubulin (Tuj1) diminishes the severity of pulmonary fibrosis

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Authors

• R Sato
• K Imamura
• T Tsukui
• Y Tomica
• K Fujino
• T Ikea
• C Combs
• M Murgai
• M Suzuki
• T Sakagami
• D Sheppered
• Y Mukouyama

Abstract

Idiopathic pulmonary fibrosis (IPF) is a devastating disease that requires an improved understanding of the pathological mechanisms for the development of novel therapies. In this study, we identified neuronal ß-III tubulin (Tuj1), a pan-neuronal marker, as a potential biomarker in pulmonary fibrosis and discovered Tuj1-expressing pericytes suppressing the severity of lung fibrosis. A series of spatial and temporal imaging and scRNA-seq analysis of bleomycin-induced fibrotic lung revealed the emergence of Tuj1-expressing pericytes in response to lung fibrosis in mice. Tuj1-expressing pericytes were also found in human IPF tissues. Our lineage-tracing experiments using the pericyte-specific CreER mice (PDGFRß-CreER or NG2-CreER) and Cre-dependent reporter mice (Rosa-LSL-YFP) supported the observation that Tuj1-expressing cells are derived from pericytes. Moreover, the combination of inflammatory and fibrotic signals such as TGF-ß1, TNFα, and IFNγ can induce Tuj1 expression in pericytes. To investigate the role of Tuj1 (gene name: Tubb3) in lung fibrogenesis, we examined what happens to fibrosis in Tubb3 knockout mice with the bleomycin administration. Interestingly, Tubb3 knockout mice exhibited enhanced lung fibrosis, accompanied by increased numbers of fibrotic fibroblasts and pro-fibrotic macrophages, without any significant neuronal abnormalities. These findings suggest that Tuj1-expressing pericytes may serve as a negative regulator in the fibrotic lung. Taken together, these studies provide a potential clue for developing a novel therapeutic strategy targeting the Tuj1-expressing pericytes in the fibrotic lung vasculature.

Scientific Focus Area: Cell Biology

This page was last updated on Monday, September 25, 2023