ClC-7在肺泡Ⅱ型细胞板层小体生物发生过程中的作用

doi:10.3870/j.issn.1672-8009.2025.06.001

医学分子生物学杂志 ›› 2025, Vol. 22 ›› Issue (6): 531-538.doi: 10.3870/j.issn.1672-8009.2025.06.001

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ClC-7在肺泡Ⅱ型细胞板层小体生物发生过程中的作用

周子旋, 郝振华, 李巍

首都医科大学附属北京儿童医院,国家儿童医学中心遗传与出生缺陷防治中心,北京市儿科研究所出生缺陷遗传学研究北京市重点实验室,儿科重大疾病研究教育部重点实验室北京市,100045

收稿日期:2025-02-10 出版日期:2025-11-30 发布日期:2025-12-25
通讯作者: 李巍(E-mail:liwei@bch.com.cn),郝振华(nanshayu@163.com)
基金资助:
国家自然科学基金(No.32293204,No.32271157)

Role of ClC-7 in Biogenesis of Lamellar Body in Alveolar Type Ⅱ Cells

ZHOU Zixuan, HAO Zhenhua, LI Wei

Beijing Children’s Hospital of Capital Medical University,Genetics and Birth Defects Control Center,National Center for Children’s Health,Beijing Key Laboratory for Genetics of Birth Defects of Beijing Pediatric Research Institute,MOE Key Laboratory of Major Diseases in Children,Beijing,100045,China

Received:2025-02-10 Online:2025-11-30 Published:2025-12-25
Contact: LI Wei(E-mail:liwei@bch.com.cn),HAO Zhenhua(E-mail:nanshayu@163.com)
Supported by:
National Natural Science Foundation of China(No.32293204,No.32271157)

摘要/Abstract

摘要： 目的探究ClC-7在板层小体(lamellar body,LB)生物发生过程中的作用以及ClC-7突变体的可能致病机制。方法使用siRNA降低A549细胞内ClC-7的表达,利用激光共聚焦显微镜以及透射电子显微镜来观察LB的形态变化。构建ClC-7野生型以及突变体质粒,观察ClC-7与LB以及其他细胞器的共定位情况。结果 ClC-7定位于LB以及溶酶体上。敲降ClC-7后的A549细胞LB体积增大。p.G203D、p.G215R、p.G292E、p.R403Q、p.L766P突变后的ClC-7主要定位到内质网,但p.P470L突变后ClC-7可以部分转运至LB。结论 A549细胞中ClC-7定位于LB与溶酶体。敲降ClC-7后LB的体积显著增大,结构异常。突变后的ClC-7多数不能正确定位在LB以及溶酶体上。

关键词: ClC-7, 板层小体, 溶酶体相关细胞器, 肺泡Ⅱ型细胞, 间质性肺病

Abstract: Objective To explore the role of ClC-7 in lamellar body(LB)biogenesis and to investigate the possible pathogenesis of some ClC-7 mutants from patients. Methods siRNA knockdown was employed to decrease the expression of ClC-7 in A549 cells,followed by observing LB morphological changes using laser confocal microscopy and transmission electron microscopy.Wild-type and mutant ClC-7 plasmids were constructed,and the co-localization of ClC-7 with LB and other organelles was observed using immunofluorescence method. Results ClC-7 was localized to LBs and lysosomes.The size of LBs in the ClC-7 knockdown cells was enlarged.Mutations of p.G203D,p.G215R,p.G292E,p.R403Q,and p.L766P,led to mislocalization of ClC-7 to the endoplasmic reticulum.Mutation of p.P470L lead to partial retention of ClC-7 on early endosomes but mostly localizes on LBs. Conclusion ClC-7 in A549 cells is localized to both LBs and lysosomes.Knockdown of ClC-7 in cultured cells leads to enlarged LBs.Most of the mutated ClC-7 cannot be correctly localized on lamellar bodies and lysosomes.

Key words: ClC-7, lamellar body, lysosome-related organelles, alveolar type Ⅱ cell, interstitial lung disease

中图分类号:

R394.3

周子旋, 郝振华, 李巍. ClC-7在肺泡Ⅱ型细胞板层小体生物发生过程中的作用[J]. 医学分子生物学杂志, 2025, 22(6): 531-538.

ZHOU Zixuan, HAO Zhenhua, LI Wei. Role of ClC-7 in Biogenesis of Lamellar Body in Alveolar Type Ⅱ Cells[J]. Journal of Medical Molecular Biology, 2025, 22(6): 531-538.

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ClC-7在肺泡Ⅱ型细胞板层小体生物发生过程中的作用

Role of ClC-7 in Biogenesis of Lamellar Body in Alveolar Type Ⅱ Cells

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