Secretoglobins SCGB3A1 and SCGB3A2 define secretory cell subsets in mouse and human airways

Secretoglobins SCGB3A1 and SCGB3A2 define secretory cell subsets in mouse and human airways
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DOI:
10.1164/rccm.200204-285oc
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发表时间:
2002-12-01
影响因子:
24.7
通讯作者:
Stripp, BR
Stripp, BR
中科院分区:
医学1区
文献类型:
--
作者:
Reynolds, SD;Reynolds, PR;Stripp, BR

文献摘要

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克拉拉细胞分泌蛋白 (CCSP) 在传导气道上皮细胞内大量表达,被认为具有免疫调节功能。小鼠和人类气道之间 CCSP 定位的差异使我们假设 CCSP 的功能同源物可能弥补近端气道位置 CCSP 表达的缺乏。我们之前鉴定了一个表达序列标签(W82219),其表达在 CCSP 敲除小鼠的 Clara 细胞内被诱导。表达的序列标签 W82219 与 CCSP 关系较远,代表分泌球蛋白新亚家族 (MmSCGB3A2) 的成员。小鼠 SCGB3 家族的另一个成员 (MmSCGB3A1) 以及人类直系同源物 (HsSCGB3A1 和 HsSCGB3A2) 与 CCSP 具有结构同源性,这表明它们可能具有共同的功能特性。 SCGB3A1 信使 RNA 定位于小鼠和新生儿肺的支气管内表达 SCGB3A2 的细胞子集。患有支气管肺发育不良的新生儿和气道损伤后的小鼠气道中的 CCSP、SCGB3A1 和 SCGB3A2 降低。我们得出的结论是,传导气道上皮的分泌细胞以部分重叠的方式表达分泌球蛋白家族的不同成员。气道疾病中分泌球蛋白表达的改变可能导致慢性气道疾病中常见的免疫调节紊乱。
Clara cell secretory protein (CCSP) is expressed abundantly within the conducting airway epithelium and is thought to have immunoregulatory functions. Differences in the localization of CCSP between mouse and human airways led us to hypothesize that functional homologues of CCSP may compensate for the lack of CCSP expression in proximal airway locations. We previously identified an expressed sequence tag (W82219) whose expression is induced within Clara cells of CCSP knockout mice. Expressed sequence tag W82219 is distantly related to CCSP and represents a member of a new subfamily of secretoglobins (MmSCGB3A2). Another member of the mouse SCGB3 family (MmSCGB3A1) as well as human orthologues (HsSCGB3A1 and HsSCGB3A2) that possess structural homology to CCSP were identified, suggesting they may share common functional properties. SCGB3A1 messenger RNA localizes to a subset of SCGB3A2-expressing cells within bronchi of both mouse and neonatal human lungs. CCSP, SCGB3A1, and SCGB3A2 were decreased in airways of neonates with bronchopulmonary dysplasia and in mice after airway injury. We conclude that secretory cells of the conducting airway epithelium express distinct members of the secretoglobin family in a partially overlapping fashion. Altered expression of secretoglobins in airway disease may contribute to immunoregulatory perturbations commonly seen in chronic airway disease.