Laminin expression in the intestine
The small intestine contains mucosal epithelial invaginations called crypts of Lieberkühn that are continuous with evaginations into the lumen called villi. The intestinal epithelium is in direct contact with a basement membrane. All laminin a-chains (laminin-111, -211, -332, -411 and -511) are expressed at significant amounts in the small intestine. Importantly, they are distributed in specific patterns along the crypt-villus axis of the intestine and are developmentally regulated (Teller et al., 2007; Lefebvre et al., 1999). The intestinal epithelia are self-renewed by a population intestinal stem cells within the intestinal crypt that give rise to progenitor cells, which can subsequently differentiate into the mature cell types (Barker, 2014).
Laminin-111 have a vital role in the early developing intestine
The α1 laminin expression is restricted to the intervillous areas in the early developing intestine and is gradually replaced by the α2 laminins as crypts begin to form. The α3 and α5 laminins were both expressed at the base of the intestinal epithelium at early stages of gut development but tend to be restricted to the villus from mid-gestation onward. The α4 laminins is not expressed in epithelial basement membrane (Teller et al., 2007).
α5 laminins are crucial for establishing and maintaining the intestinal architecture
The villus basement membrane is rich in laminin α5 which is crucial for both establishing and maintaining the small intestinal crypt-villus architecture (Mahoney et al., 2008; Ritié et al., 2011). In a publication by Ritié et al., the authors describe a mechanistic link between laminin α5 gene deficiency and the physiological phenotype showing that laminin a5 plays a crucial role in both epithelial and mesenchymal cell behavior by regulating Wnt and PI3K signaling (Ritié et al., 2011). It's concluded that laminin-511 stimulates expression and activity of the survival factor Akt and stimulate cell adhesion, migration as well as epithelial differentiation (Ritié et al., 2011). In the absence of laminin α5, the proliferative compartment of the intestine expands, suggesting a delay in initiating differentiation (Mahoney et al., 2008). Lack of the laminin α5 chain was accompanied by a decrease in epithelial α3β1 integrin and the Lutheran receptor, indicating that those are likely targets for the laminin α5 laminins (Bolcato-Bellemin et al., 2003). The B4 integrin is also expressed in the Enterocytes differentiated normally in the absence of laminin α5 but the terminal differentiation of goblet cells was affected, as shown by the increased numbers of intermediate cells and alteration of mucous granules towards the colon type (Mahoney et al., 2008). The α5 laminins has also shown to a major role in intestinal smooth muscle organization and differentiation (Bolcato-Bellemin et al., 2003).
We recommend laminin-111 (LN111) for early intestinal specification and laminin-511 (LN511) for maturation and maintenance.
- Laminin α5 influences the architecture of the mouse small intestinal mucosa. Mahoney et al., J Cell Sci., 2008
- Abnormal Wnt and PI3Kinase Signaling in the Malformed Intestine of lama5 Deficient Mice. Ritié et al. PLOS ONE, 2012
- Laminins in the Developing and Adult Human Small Intestine: Relation With the Functional Absorptive Unit. Teller et al., Developmental dynamics, 2007
- Developmental expression and cellular origin of the laminin alpha2, alpha4, and alpha5 chains in the intestine. Lefebvre et al., Dev Biol., 1999
- Laminin α5 chain is required for intestinal smooth muscle development. Bolcato-Bellemin et al., Developmental biology, 2003
- Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration. Barker. Nat Rev Mol Cell Biol., 2014