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Identification and functional characterization of a novel surfactant protein A2 mutation (p.N207Y) in a Chinese family with idiopathic pulmonary fibrosis.

ABSTRACT: BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is a serious disorder with a high mortality rate worldwide. It is characterized by irreversible scarring of the lung parenchyma resulting from excessive collagen production by proliferating fibroblasts/myofibroblasts. Previous studies have revealed that mutations in surfactant protein-related genes and telomerase complex genes are crucial underlying genetic factors. METHODS:In this study, we enrolled a family with IPF from the central southern region of China. Whole-exome sequencing was employed to explore candidate genes in this family. Real-time PCR and western blotting were used to study the functions of the identified mutations in vitro. RESULTS:A novel mutation (NM_001098668.4: c.619A>T; NP_001092138.1: p.N207Y) in surfactant protein A2 (SFTPA2,), having not been previously reported to be a mutation, was identified and co-separated with all affected individuals in the IPF family. Functional research further revealed that the novel mutation affects the secretion of SFTPA2 protein and induces endoplasmic reticulum stress as well as apoptosis in A549 cells. CONCLUSION:We are confident that this novel mutation (NM_001098668.4: c.619A>T; NP_001092138.1: p.N207Y) in SFTPA2 is the genetic mutation of the IPF family. Our study not only confirms the importance of SFTPA2 in IPF but also expands the spectrum of SFTPA2 mutations and contributes to the genetic diagnosis and counseling of IPF patients.

SUBMITTER: Liu L

PROVIDER: S-EPMC7507553 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Identification and functional characterization of a novel surfactant protein A2 mutation (p.N207Y) in a Chinese family with idiopathic pulmonary fibrosis.

Liu Lv L Qin Jieli J Guo Ting T Chen Ping P Ouyang Ruoyun R Peng Hong H Luo Hong H

Molecular genetics & genomic medicine 20200630 9

<h4>Background</h4>Idiopathic pulmonary fibrosis (IPF) is a serious disorder with a high mortality rate worldwide. It is characterized by irreversible scarring of the lung parenchyma resulting from excessive collagen production by proliferating fibroblasts/myofibroblasts. Previous studies have revealed that mutations in surfactant protein-related genes and telomerase complex genes are crucial underlying genetic factors.<h4>Methods</h4>In this study, we enrolled a family with IPF from the central ...[more]

PMID: 32602668

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Project description:BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive, eventually fatal disease. IPF is characterized by excessive accumulation of the extracellular matrix (ECM) in the alveolar parenchyma and progressive lung scarring. The pathogenesis of IPF and whether the ECM involved in the process remain unknown.MethodsTo identify potential treatment target and ECM associated proteins that may be involved in the development of IPF, we employed isobaric tag for relative and absolute quantitation (iTRAQ) combined liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach to examine protein expression in lung tissues from IPF patients.ResultsA total of 662 proteins with altered expression (455 upregulated proteins and 207 downregulated proteins) were identified in lung tissue of IPF patients compared with control. KEGG pathway enrichment analysis showed that the altered proteins in lung tissue mainly belonged to the PI3K-Akt signaling, focal adhesion, ECM-receptor interaction, and carbon metabolism pathways. According to the bioinformatic definition of the matrisome, 229 matrisome proteins were identified in lung tissue. These proteins comprised the ECM of lung, of which 104 were core matrisome proteins, and 125 were matrisome-associated proteins. Of the 229 ECM quantified proteins, 56 significantly differentially expressed proteins (19 upregulated proteins and 37 downregulated proteins) were detected in IPF lung tissue samples. In addition to proteins with well-known functions such as COL1A1, SCGB1A1, TAGLN, PSEN2, TSPAN1, CTSB, AGR2, CSPG2, and SERPINB3, we identified several novel ECM proteins with unknown function deposited in IPF lung tissue including LGALS7, ASPN, HSP90AA1 and HSP90AB1. Some of these differentially expressed proteins were further verified using Western blot analysis and immunohistochemical staining.ConclusionsThis study provides a list of proteomes that were detected in IPF lung tissue by iTRAQ technology combined with LC-MS/MS. The findings of this study will contribute better understanding to the pathogenesis of IPF and facilitate the development of therapeutic targets.

Dataset Information

Identification and functional characterization of a novel surfactant protein A2 mutation (p.N207Y) in a Chinese family with idiopathic pulmonary fibrosis.

Publications

Identification and functional characterization of a novel surfactant protein A2 mutation (p.N207Y) in a Chinese family with idiopathic pulmonary fibrosis.

Similar Datasets

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