A recent study by Dr. David Schwartz of University of Colorado showed that a SNP in the promoter region of MUC5B is strongly associated with FPF and IPF [1]. The odds ratios for disease among subjects who were heterozygous and those who were homozygous for the minor allele of this SNP (rs35705950) were 6.8 and 20.8, respectively, for FPF. The odds ratios for IPF were similar (9.0 and 21.8). MUC5B expression in the lung was 14.1 times as high in subjects with IPF as in those healthy donors.
The significance of the study, along with previous reports that variants in SFTPA, SFTPB, SFTPC, ABCA1, and ABCA3 were found in patients with pulmonary fibrosis, points to a plausible notion that the dysregulated secretion of lung surfactants and mucins by airway and alveolar epithelial cells leads to endoplasmic-reticulum (ER) stress. ER stress is found in alveolar epithelial cells in IPF [2]. However, we do not know the dysregulation of these proteins is duo to a common set of transcription factors or to epigenetic regulations.
[1] Seibold MA, et al. A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med. 2011 Apr 21;364(16):1503-12. PubMed PMID: 21506741.
[2] Korfei M, et al. Epithelial endoplasmic reticulum stress and apoptosis in sporadic idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2008 Oct 15;178(8):838-46. Epub 2008 Jul 17. PubMed PMID: 18635891; PubMed Central PMCID: PMC2566794.
The significance of the study, along with previous reports that variants in SFTPA, SFTPB, SFTPC, ABCA1, and ABCA3 were found in patients with pulmonary fibrosis, points to a plausible notion that the dysregulated secretion of lung surfactants and mucins by airway and alveolar epithelial cells leads to endoplasmic-reticulum (ER) stress. ER stress is found in alveolar epithelial cells in IPF [2]. However, we do not know the dysregulation of these proteins is duo to a common set of transcription factors or to epigenetic regulations.
[1] Seibold MA, et al. A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med. 2011 Apr 21;364(16):1503-12. PubMed PMID: 21506741.
[2] Korfei M, et al. Epithelial endoplasmic reticulum stress and apoptosis in sporadic idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2008 Oct 15;178(8):838-46. Epub 2008 Jul 17. PubMed PMID: 18635891; PubMed Central PMCID: PMC2566794.
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