Fibroblasts form a subepithelial network in the gastrointestinal tract. Furuya et al. propose that this fibroblast network serves as a mechanosensor for the intestine. Using subepithelial cells cultured from rat duodenum, the authors showed that these cells predominantly express P2Y1 receptors for adenosine triphosphate (ATP) and that application of ATP to flattened cells resulted in calcium signal; pharmacological analysis was consistent with P2Y1 receptors mediating this response. Touching the flattened cells with a thin glass rod caused an increase in intracellular calcium concentration in the touched cell, and this calcium transient propagated to surrounding cells (both those in contact with the touched cell and those not in direct contact). The cells also exhibited touch-induced contractions. Cell stretching also triggered an increase in calcium concentration and stimulated an increase in extracellular ATP that increased with increasing stretch applied. When the cells were treated with dibutyryl cyclic adenosine 3′,5′-monophosphate (dbcAMP) to increase intracellular cAMP concentrations, the cells became stellate shaped and did not respond to touch or stretch, which appeared to be due to both decreased ATP release and decreased sensitivity to ATP. To support a model describing the fibroblasts as the mechanosensors that stimulate the enteric nerves of the villi, the authors cocultured the subepithelial fibroblasts with neural NG108-15 cells and found that touching the fibroblasts induced a calcium wave in both the fibroblast and neural cells. Thus, the authors suggest that an additional role for the subepithelial fibroblast network is a mechanosensor for the intestinal villi that releases ATP, which stimulates both the fibroblast network and the nearby sensory neurons.
K. Furuya, M. Sokabe, S. Furuya, Characteristics of subepithelial fibroblasts as a mechano-sensor in the intestine: Cell shape-dependent ATP release and P2Y1 signaling. J. Cell. Sci. 118, 3289-3304 (2005). [Abstract] [Full Text]