Differential expression of laminins and their integrin receptors in developing and adult human lung.

Abstract

Laminins (Ln) appear to play an important role in the morphogenesis of airways. We studied the expression of different laminin chains and their integrin receptors in fetal and adult lung by immunohistochemistry. Special attention was focused on the changes in the expression of these proteins during the development from the pseudoglandular (PG) and canalicular stages to adult lung, and on the possible implications of the changes for the normal lung development. The most significant changes in the expression pattern were found during the development from the PG stage to the canalicular stage. Basement membranes (BM) of both the epithelial buds and the becoming bronchi showed reactivity for Ln-alpha 1, -alpha 3, and -beta 3 chains at all stages. The alpha 2 chain was expressed only in the epithelial buds at the PG stage, and could not be found in any epithelial structures at the canalicular stage. Similarly, at the PG stage the Ln-beta 2 chain was expressed in BMs of both epithelial buds and bronchi but disappeared from the bronchial BM before the canalicular stage. Ln-beta 1 chain appeared in the bronchial BM first in the mature lung, which suggests the presence of uncharacterized Ln-beta chains earlier in development. There were considerable changes in the expression of integrins (Int) concomitantly with alterations in the composition of the BMs. At the PG stage the epithelial buds showed reactivity for Int-alpha 2 -alpha 3, and -alpha 6 subunits, but at the canalicular stage the Int-alpha 2 and -alpha 6 subunits disappeared, and only Int-alpha 3 integrin subunit was found in evolving alveolar walls; Int-alpha 6 was found in capillaries. A similar distribution of Int subunits was also found in adult alveoli. The bronchi expressed Int-alpha 2, -alpha 3, and -alpha 6 subunits at all developmental stages, but the Int-beta 4 subunit emerged first at the canalicular stage. Our results suggest that there are major changes in the expression of Ln and their Int receptors during morphogenesis of the lung, which may be important for normal development.

Laminin Isoforms in Fetal and Adult Human Adrenal Cortex

“…They form a growing protein family consisting of at least of 14 trimeric proteins and containing ␣-, ␤-, and ␥-chains; at present, five ␣-, three ␤-, and three ␥-chains have been described (11,12). Different Ln isoforms show distinct localizations in various organs, such as stomach and airways (13,14), suggesting organ-or tissue-specific functions. Immunolocalization studies have revealed a complex Ln composition in BM of many epithelial tissues.…”

Laminin-6 assembles into multimolecular fibrillar complexes with perlecan and participates in mechanical-signal transduction via a dystroglycan-dependent, integrin-independent mechanism

“…Specifically, several laminin subunits have been identified in the matrix-rich basement membrane of AECs in vivo (Coraux et al, 2002;Mizushima et al, 1998;Pierce et al, 1998;Virtanen et al, 1996). This basement membrane is covered by a sheet of cells composed mainly of type-I (AT1, alveolar type-I pneumocytes) cells (Crapo et al, 1982).…”

“…The type-II cells produce surfactant, proliferate and differentiate into type I cells (Crapo et al, 1982;Fehrenbach, 2001;Uhal, 1997). In the basement membrane of the lung, subunits of laminin show precise, developmentally regulated patterns of expression (Coraux et al, 2002;Mizushima et al, 1998;Pierce et al, 1998;Virtanen et al, 1996). For example, laminin α1 expression is restricted to early human lung morphogenesis, whereas the laminin α5 is continuous from early lung development to adult life (Pierce et al, 1998;Virtanen et al, 1996).…”

“…In the basement membrane of the lung, subunits of laminin show precise, developmentally regulated patterns of expression (Coraux et al, 2002;Mizushima et al, 1998;Pierce et al, 1998;Virtanen et al, 1996). For example, laminin α1 expression is restricted to early human lung morphogenesis, whereas the laminin α5 is continuous from early lung development to adult life (Pierce et al, 1998;Virtanen et al, 1996). Moreover, the α3 laminin subunit is expressed in the basement membrane of the alveoli of adult rat lung, where it localizes with β1, γ1 and β2 subunits.…”

Overexpression of β3/γ2 chains of laminin-5 and MMP7 in biliary cancer

“…Expression of the three subunits of LN5 is regulated differentially in cancer cell lines and in normal and malignant tissues including HCC [9][10][11] . Indeed, LNγ2 has been shown to be secreted as a single subunit in gastric cancer [12] .…”