Targeting Cx43 and N-cadherin, which are abnormally upregulated in venous leg ulcers, influences migration, adhesion and activation of Rho GTPases.

ABSTRACT:

Background

Venous leg ulcers can be very hard to heal and represent a significant medical need with no effective therapeutic treatment currently available.

Principal findings

In wound edge biopsies from human venous leg ulcers we found a striking upregulation of dermal N-cadherin, Zonula Occludens-1 and the gap junction protein Connexin43 (Cx43) compared to intact skin, and in stark contrast to the down-regulation of Cx43 expression seen in acute, healing wounds. We targeted the expression of these proteins in 3T3 fibroblasts to evaluate their role in venous leg ulcers healing. Knockdown of Cx43 and N-cadherin, but not Zonula Occludens-1, accelerated cell migration in a scratch wound-healing assay. Reducing Cx43 increased Golgi reorientation, whilst decreasing cell adhesion

SUBMITTER: Mendoza-Naranjo A 

PROVIDER: S-EPMC3352877 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature