Abstract
BackgroundClaudins are the main components of tight junctions, structures which are associated with cell polarity and permeability. The aim of this study was to analyze the expression of claudins 1, 3, 4, 5, and 7 in developing human lung tissues from 12 to 40 weeks of gestation.Methods47 cases were analyzed by immunohistochemisty for claudins 1, 3, 4, 5 and 7. 23 cases were also investigated by quantitative RT-PCR for claudin-1, -3 and -4.ResultsClaudin-1 was expressed in epithelium of bronchi and large bronchioles from week 12 onwards but it was not detected in epithelium of developing alveoli. Claudin-3, -4 and -7 were strongly expressed in bronchial epithelium from week 12 to week 40, and they were also expressed in alveoli from week 16 to week 40. Claudin-5 was expressed strongly during all periods in endothelial cells. It was expressed also in epithelium of bronchi from week 12 to week 40, and in alveoli during the canalicular period. RT-PCR analyses revealed detectable amounts of RNAs for claudins 1, 3 and 4 in all cases studied.ConclusionClaudin-1, -3, -4, -5, and -7 are expressed in developing human lung from week 12 to week 40 with distinct locations and in divergent quantities. The expression of claudin-1 was restricted to the bronchial epithelium, whereas claudin-3, -4 and -7 were positive also in alveolar epithelium as well as in the bronchial epithelium. All claudins studied are linked to the development of airways, whereas claudin-3, -4, -5 and -7, but not claudin-1, are involved in the development of acinus and the differentiation of alveolar epithelial cells.
Highlights
During lung ontogenesis, the conducting airways are quite early lined by epithelium which consists of ciliated, secretory, intermediate and basal cells [1,2]
Epithelial cell differentiation is closely connected to the changes in the extracellular matrix and its proteins which are expressed in varying amounts and in distinct locations during human lung development [4,5]
Claudin-5 was strongly positive in endothelial cells, and it was weakly positive in bronchi, bronchioles and small developing airways (Fig 1F)
Summary
The conducting airways are quite early lined by epithelium which consists of ciliated, secretory, intermediate and basal cells [1,2]. The epithelium of distal lung including type I and II pneumocytes and Clara cells lining the walls of respiratory bronchioles and alveoli, differentiate later than the cells of the conducting airways [3]. Connexin 26, which is an element of the gap junctions, has been shown to be expressed in developing and adult human lung tissues [14]. The aim of this study was to analyze the expression of claudins 1, 3, 4, 5, and 7 in developing human lung tissues from 12 to 40 weeks of gestation
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