Role for gap junctional intercellular communications in wound repair.

Abstract

The participation of fibroblasts in wound repair is a coordinated effort requiring sequential cellular modulations to behavior including migration (entering), proliferation (increasing cell numbers), synthesis (depositing a collagen matrix), remodeling (organizing collagen), transformation into myofibroblasts, apoptosis, and elimination. Disruptions in that orderly sequence of behaviors will alter repair. Insights into controlling wound repair have focused on soluble factors such as cytokines and growth factors. Here we examine the direct communications between coupled cells through gap junctional intercellular communications. Molecules of less than 1000 MW pass directly between cells through gated gap junction channels. Sugars, amino acids, and oxygen, as well as second messengers such as cAMP, inositol phosphates, and calcium can pass directly between coupled cells. Does gap junctional intercellular communication affect fibroblast phenotype progression in granulation tissue maturation? In rats gap junctional intercellular communication uncouplers heptanol and endosulfan were injected daily into polyvinyl alcohol sponge implants. At 7 days, uncoupler-treated implants had capsules with increased fibroblast density, reduced cell penetration into the sponge, and diminished numbers of myofibroblasts. By polarized light, the uncouplers reduced the deposition and organization of collagen and thereby disrupted the coordinated phenotypic changes seen in fibroblasts during the repair process. It is proposed that gap junctional intercellular communication is critical for fibroblast progression from migratory cell to apoptosis as granulation tissue matures into scar.