MUC5B
MUC5B encodes a structurally related, gel-forming mucin glycoprotein and supports airway mucus barrier function through mucociliary clearance (MCC)[1]. Mechanistically, mouse Muc5b, but not Muc5ac, is required for MCC, airway infection control, middle-ear infection control, and immune homeostasis[1]. In muco-obstructive lung disease models, Muc5b absence reduced MCC and mucus plugging, yet complete removal increased airway inflammation, making full inhibition biologically risky[2]. In pulmonary fibrosis, the MUC5B promoter variant rs35705950 associates with familial interstitial pneumonia and idiopathic pulmonary fibrosis, and lung MUC5B expression increases in idiopathic pulmonary fibrosis tissue[3]. Distal-airspace Muc5b overexpression in mice impaired MCC and enhanced bleomycin-induced lung fibrosis, supporting use of Muc5b-overexpressing fibrosis models for mechanistic studies[4]. Compared with related isoform MUC5AC, MUC5B shows stronger evidence for MCC and host-defense dependence, whereas increased MUC5AC, not MUC5B, predicted COPD progression in SPIROMICS[1][5]. For experimental applications, the mucolytic P-2119 reduced MUC5B molecular mass, lowered mucus viscosity, restored MCC, and reduced bleomycin-induced fibrosis in Muc5b-overexpressing mice[4].
References:
- [1]. Roy MG, et al. Muc5b is required for airway defence. Nature. 2014 Jan 16;505(7483):412-6. [Content Brief]
- [2]. Livraghi-Butrico A, et al. Contribution of mucus concentration and secreted mucins Muc5ac and Muc5b to the pathogenesis of muco-obstructive lung disease. Mucosal Immunol. 2017 Mar;10(2):395-407. [Content Brief]
- [3]. Seibold MA, et al. A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med. 2011 Apr 21;364(16):1503-12. [Content Brief]
- [4]. Hancock LA, et al. Muc5b overexpression causes mucociliary dysfunction and enhances lung fibrosis in mice. Nat Commun. 2018 Dec 18;9(1):5363. [Content Brief]
- [5]. Radicioni G, et al. Airway mucin MUC5AC and MUC5B concentrations and the initiation and progression of chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort. Lancet Respir Med. 2021 Nov;9(11):1241-1254. [Content Brief]
