Background: Surfactant protein C (SP-C) is a hydrophobic protein produced exclusively by type II alveolar epithelial cells (AECs) and plays an important role in the modulation of lung mechanics by its direct effects on alveolar surface tension. The SP-C gene (SFTPC) encodes precursor SP-C (proSP-C) containing four distinct structural and functional domains, a short cytoplasmic N-terminal domain (residues 1-23), a mature domain (residues 24-58), a non-BRICHOS region (residues 59-89), and a BRICHOS domain (residues 90-197).
Interstitial lung disease (ILD) in infants and children are mostly chronic and associated with high morbidity and mortality. Mutations in the SFTPC have recently been linked to ILD associated with abnormal expression of SP-C. Previous studies showed that mutations involving non-BRICHOS and BRICHOS domains of proSP-C may represent different pathogenesis of ILD. However, the pathway and mechanism of mutations located within mature domain of proSP-C remain unclear.
In the present study, we described a novel heterozygous SFTPC mutation located in the mature domain of proSP-C in a Japanese girl associated with ILD, and investigated whether the novel proSP-CL55F showed alteration of subcellular localization in human type II lung epithelial cell line (A549).
背景:サーファクタント・タンパク質C(SP-C)は、Ⅱ型肺胞上皮細胞により排他的に作られた疎水性タンパク質で、肺胞表面張力の直接効果による肺機能の調節に重要な役割を果たします。SP-C遺伝子(SFTPC)は、4つの構造的に異なった機能ドメインや短細胞質Nターミナルドメイン(残留物 1-23)、マチュアドメイン(残留物 24-58)、非ブリコス領域(残留物 59-89)、ブリコスドメイン(残留物 90-197)を含んだ前駆SP_C(proSP-C)をエンコードします。
 現在の研究では、私たちは新異型接合のSFTPC突然変異がILDに関連のある日本人女児のproSP-Cのマチュアドメインにあると説明しており、新型proSP-CL55F が人間タイプⅡ軟膏上皮細胞株(A-549)の中で細胞内位置特定の変化を示すか示さないかを研究した。