MISC

2011年10月

Surfactant protein C G100S mutation causes familial pulmonary fibrosis in Japanese kindred

EUROPEAN RESPIRATORY JOURNAL
  • S. Ono
  • ,
  • T. Tanaka
  • ,
  • M. Ishida
  • ,
  • A. Kinoshita
  • ,
  • J. Fukuoka
  • ,
  • M. Takaki
  • ,
  • N. Sakamoto
  • ,
  • Y. Ishimatsu
  • ,
  • S. Kohno
  • ,
  • T. Hayashi
  • ,
  • M. Senba
  • ,
  • M. Yasunami
  • ,
  • Y. Kubo
  • ,
  • L. M. Yoshida
  • ,
  • H. Kubo
  • ,
  • K. Ariyoshi
  • ,
  • K. Yoshiura
  • ,
  • K. Morimoto

38
4
開始ページ
861
終了ページ
869
記述言語
英語
掲載種別
DOI
10.1183/09031936.00143610
出版者・発行元
EUROPEAN RESPIRATORY SOC JOURNALS LTD

Several mutations in the surfactant protein C (SP-C) gene (SFTPC) have been reported as causing familial pulmonary fibrosis (FPF). However, the genetic background and clinical features of FPF are still not fully understood.
We identified one Japanese kindred, in which at least six individuals over three generations were diagnosed with pulmonary fibrosis. We examined the patients radiologically and histopathologically and sequenced their SFTPC and ABCA3 genes. We also established a cell line stably expressing the mutant gene.
All the patients had similar radiological and histopathological characteristics. Their histopathological pattern was that of usual interstitial pneumonia, showing numerous fibroblastic foci even in areas without abnormal radiological findings on chest high-resolution computed tomography. No child had respiratory symptoms in the kindred. Sequencing of SFTPC showed a novel heterozygous mutation, c.298G>A (G100S), in the BRICHOS domain of proSP-C, which co-segregated with the disease. However, in the ABCA3 gene, no mutation was found. In vitro expression of the mutant gene revealed that several endoplasmic reticulum stress-related proteins were strongly expressed.
The mutation increases endoplasmic reticulum stress and induces apoptotic cell death compared with wild-type SP-C in alveolar type II cells, supporting the significance of this mutation in the pathogenesis of pulmonary fibrosis.

Web of Science ® 被引用回数 : 57

リンク情報
DOI
https://doi.org/10.1183/09031936.00143610
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/21828032
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000295410200017&DestApp=WOS_CPL
URL
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=80053546689&origin=inward
ID情報
  • DOI : 10.1183/09031936.00143610
  • ISSN : 0903-1936
  • PubMed ID : 21828032
  • SCOPUS ID : 80053546689
  • Web of Science ID : WOS:000295410200017

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