Expression and function of the Transforming Growth Factor-b system in the human and rat enteric nervous system.

BACKGROUND

Transforming growth factor-betas (TGF-bs) are pleiotropic growth factors exerting neurotrophic functions upon various neuronal populations of the central nervous system. In contrast, the role of TGF-b isoforms in the enteric nervous system (ENS) is largely unknown. We therefore analyzed the gene expression pattern of the TGF-b system in the human colon and in rat myenteric plexus, and smooth muscle cell cultures and determined the effect of TGF-b isoforms on neuronal differentiation.

METHODS

Human colonic samples as well as cultured rat myenteric plexus, and smooth muscle cells were assessed for mRNA expression levels of the TGF-b system (TGF-b1-3, TbR-1-3) by qPCR. The colonic wall was separated into mucosa and tunica muscularis and enteric ganglia were isolated by laser microdissection (LMD) to allow site-specific gene expression analysis. Effects of TGF-b isoforms on neurite outgrowth and branching pattern of cultured myenteric neurons were monitored.

KEY RESULTS

mRNA expression of the TGF-b system was detected in all compartments of the human colonic wall as well as in LMD-isolated myenteric ganglia. Cultured myenteric neurons and smooth muscle cells of rat intestine also showed mRNA expression of all ligands and receptors. Transforming growth factor-b2 treatment increased neurite length and branching pattern in cultured myenteric neurons.

CONCLUSIONS & INFERENCES: The TGF-b system is abundantly expressed in the human and rat ENS arguing for an auto-/paracrine function of this system on enteric neurons. Transforming growth factor-b2 promotes neuronal differentiation and plasticity characterizing this molecule as a relevant neurotrophic factor for the ENS.