Secretoglobins SCGB3A1 and SCGB3A2 Define Secretory Cell Subsets in Mouse and Human Airways

Abstract

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.

Differential expression of chitinases identify subsets of murine airway epithelial cells in allergic inflammation

“…Regionally specialized secretory activity is suggested by variation in the number, density, and morphological characteristics of secretory granules and granular endoplasmic reticulum, differences in cytoplasmic and granular CCSP concentration, and in resynthesis of CCSP after induced secretion (3,12,13,35,51). In addition to quantitative differences in CCSP expression, qualitative molecular differences exist as well, since secretoglobulin 3A1, a gene product related to CCSP, is expressed by proximal but not distal airway secretory cells (42). Differences in CYP450 enzymatic activity, cellular glutathione pool size, and glutathione regenerative capacity further distinguish these cells and may contribute to variation in pollutant sensitivity (14,17,34,37,55,56).…”

Airway Epithelial Stem Cells and the Pathophysiology of Chronic Obstructive Pulmonary Disease

“…Secretoglobin (SCGB) 1a1, also known as CC10 or CCSP, is a member of the SCGB family that has been widely used as a marker for Clara cells. Several different SCGBs are also expressed in the airway epithelium (67). SCGB1a1 is expressed in human upper airway secretory cells that do not appear to proliferate (68).…”

Induction of Uteroglobin-Related Protein 2 (Ugrp2) Gene Expression by the Th2 Cytokines IL-4 and IL-13

“…In contrast, Ugrp2 expression in mice is predominantly found in trachea and lung (3,5), with low levels of expression reported in other tissues, such as heart, stomach, small intestine, and mammary gland (5). Ugrp2 mRNA is detected on embryonic day 17.5 during mouse development in the tracheal epithelium and later also in the submucosal glands of the proximal trachea and bronchi (4,5). Ugrp2 mRNA expression is up-regulated by retinoic acid, which induces mucinous differentiation in primary normal human bronchial epithelial cells (5).…”

“…Mouse UGRP2 shows 33% amino acid sequence identity to mouse UGRP1 (2). Based on amino acid sequences, both UGRP1 and UGRP2 belong to a gene superfamily of the uteroglobin/Clara cell secretory proteins (UG/CCSP), officially termed secretoglobins (3)(4)(5).…”