Laminin expression in lung
Laminin are key proteins in the basement membranes of the airway and alveolar epithelium, endothelium, bronchial and vascular smooth muscle cells, nerve cells, and visceral pleura. Laminins are crucial for lung development where different laminin isoforms exhibit specific, non-overlapping functions. All five laminin α chains are present during early embryonic lung development but normal adult lung tissue contains primarily laminin α3, α4, and α5 chains (Miner et al,1997). Laminins α1, α2, and α3 are co-localized to the airway epithelial basement membrane during early lung development. Laminin α4 is seen in pericellular basement membrane of smooth muscle cells lining the airway epithelium (Nguyet and Senior, 2006). Laminin α4 and α5 are also expressed in vascular endothelial basement membrane in late embryonic lungs. Laminin α5 also co-localizes with laminins α1–α3 in the BM of airway epithelium and it is the only laminin α chain found in the visceral pleural basement membrane (Nguyet and Senior, 2006).
Laminin-111 and laminin-521 play a role in early and late lung development
It has become evident that laminin α1 and laminin α5 have central roles in the development of the human lung. Laminin α1 expression is restricted to early human lung morphogenesis, whereas the expression of laminin α5 in human lung is continuous from early lung development through adult life (Pierce et al., 2000). Laminin-111, expressed by epithelial and mesenchymal cells in the mouse developing lung, plays a role in branching morphogenesis and in epithelial cell polarity (Schuger et al., 1990a; Schuger et al., 1990b; Schuger et al., 1991; Schuger et al., 1997) whereas laminin-211 and -221 have a role in smooth muscle cell differentiation. In developing human lung, Virtanen et al. found that the most significant changes in laminin and integrin expression pattern were found during the development from the pseudoglandular stage to the canalicular stage (Virtanen et al., 1996). Expression of laminin α5 begins in early lung development and persists into adulthood with a widespread expression. In the lung, laminin α5 is present in airway, alveolar, endothelial, and visceral pleura BMs. Studies of laminin α5-deficient mice indicate that laminins-511 and -521 are essential for normal lobar septation in early lung development and normal alveolization and distal epithelial cell differentiation and maturation in late lung development (Nguyet et al, 2005). Laminin-332 is well associated with cutaneous epithelial cell functions, however, laminin γ2 null mice have only minimal changes in lung development, and it’s suggested that laminin-332 in lung have a role in response to injury or disease processes. Laminin α2 and α4 null mice survive to adulthood and have no do not have obvious lung abnormalities (Nguyet and Senior, 2006).
Laminin-integrin interactions regulates lung branching morphogenesis
Lung branching morphogenesis likely involves integrin interactions with laminins. The integrin α6 null mouse does not have a reported lung phenotype, however integrin α3/integrin α6 double knockout mice have several features reminiscent of the laminin α5 knockout (De Arcangelis et al., 1999). However, branching morphogenesis is not affected in laminin α5, γ2, or α3 knockouts even though integrins α3 and α6 are the primary adhesive receptors for α3 and α5 laminins. Since, laminin-111 has been shown to play a role in branching morphogenesis, it has been suggested that laminin-111 could be central for this integrin interaction (Nguyet and Senior, 2006).
We recommend laminin-111 (LN111) for early lung specification and laminin-521 (LN521) for maturation.
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