Depletion of Numb and Numblike in Murine Lung Epithelial Cells Ameliorates Bleomycin-Induced Lung Fibrosis by Inhibiting the β-Catenin Signaling Pathway

• DOI: 10.3389/fcell.2021.639162
• Publication Date: 2021-05-26T05:38:17Z
• Authors: Alessandro Ianni; Michael Hofmann; Poonam Kumari; Shahriar Tarighi; Hamza M Al-Tamari; André Görgens; Bernd Giebel; Hendrik Nolte; Marcus Krüger; Isabelle Salwig; Soni Savai Pullam...; Andreas Günther; André Schneider; Thomas Braun
• Keywords: NUMB; Myofibroblast

Idiopathic pulmonary fibrosis (IPF) represents the most aggressive form of (PF) and is a highly debilitating disorder with poorly understood etiology. The lung epithelium seems to play critical role in initiation progression disease. A repeated injury epithelial cells prompts type II alveolar secrete pro-fibrotic cytokines, which induces differentiation resident mesenchymal stem into myofibroblasts, thus promoting aberrant deposition extracellular matrix (ECM) formation fibrotic lesions. Reactivation developmental pathways such as Wnt-β-catenin signaling cascade plays this process, but underlying mechanisms are still enigmatic. Here, we demonstrate that membrane-associated protein NUMB required for pathological activation β-catenin following bleomycin-induced injury. Importantly, depletion Numb Numblike reduces accumulation lesions, preserves functions, increases survival rates after bleomycin treatment mice. Mechanistically, interacts casein kinase 2 (CK2) relies on CK2 activate signaling. We propose pharmacological inhibition may represent an effective strategy development novel therapeutic approaches against PF.