Laminin‐2 stimulates the proliferation of epithelial cells in a conjunctival epithelial cell line

Abstract

Laminin-2 (LN-2, alpha2beta1gamma1) is a basement membrane-associated laminin isoform usually considered in the context of muscle and nerve tissues. To test the hypothesis that LN-2 can additionally modulate epithelial cell biology, an analysis of the role of LN-2 in cell adhesion, activation of signalling intermediates and proliferation was undertaken. A virally transformed human conjunctival epithelial cell line (HC0597) was utilized in this study. Adhesion assays using function-inhibiting antibodies demonstrated that alpha3beta1 integrin is essential for the rapid attachment of conjunctival epithelial cells to LN-2. Bromodeoxyuridine (BrdU) incorporation analyses revealed that, compared with LN-1 or LN-10, LN-2 significantly promotes epithelial proliferation. Phosphorylation of the signalling intermediates Erk1/2 and Akt-1 was observed within 15 min of cell adhesion to LN-2. Inhibiting alpha3beta1 integrin function decreased total cellular phosphotyrosine levels, specifically inhibited phosphorylation of Erk1/2 and Akt-1, and dampened the proliferation response of epithelial cells adherent to LN-2. Inhibition of Erk or Akt activation inhibited cell proliferation in a dose-dependent manner. However, the inhibition of Erk resulted in a stronger suppression of proliferation compared with Akt inhibition. From these results, it is concluded that human conjunctival epithelial cells adhere to immobilized LN-2 using alpha3beta1 integrin. alpha3beta1 integrin/LN-2 signalling, transduced primarily through an Erk pathway, enhances epithelial cell proliferation. These results demonstrate that LN-2 can impact on epithelial cell biology in addition to nerve and muscle, and provide information regarding the role of this isoform in ocular surface epithelial cells.

Laminin isoforms: biological roles and effects on the intracellular distribution of nuclear proteins in intestinal epithelial cells

“…It is worth noting that the changes of the subcellular localisation of the nuclear proteins in cells cultured on laminin-1 and the other laminins well correlate the previously described modifications between differentiating versus proliferative Caco2/ TC7 cells cultured on plastic [9]. Furthermore, our observations are in accordance with published data as enhanced proliferation has been reported for laminin-2 in human epithelial conjunctival cells [44], for laminin-5 in embryonic kidney cells [45], and for laminin-10 in keratinocytes [46] or hematopoietic progenitor cells [47].…”

Infected epithelial inclusion cyst mimicking subconjunctival abscess after strabismus surgery

“…[4][5][6] The rapidity with which the cyst formed in our case may have been related to Staphylococcus aureus colonization. Staphylococcus aureus is known to adhere to conjunctival laminin basement membrane proteins responsible for epithelial proliferation 7,8 ; this adherence, in addition to inflammatory stimulation, may have promoted rapid epithelial cell growth. The partially-formed cyst had a pathway to the ocular surface via the suture tract, which allowed an outlet for pus drainage.…”

Laminin α5 influences the architecture of the mouse small intestine mucosa

“…Our data do suggest that laminins, in the context of the BM, regulate tissue patterning and remodeling by fine-tuning intestinal epithelial cell behavior. The crypt restricted deposition of laminin α2 is consistent with its function in promoting cell proliferation in vitro (Dowgiert et al, 2004). The abrupt onset of laminin α5 deposition at the crypt-villus junction and its abundance in the villus subepithelial BM suggest a role in inducing cell differentiation.…”