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Fig. 12. A model for subepithelial fibroblasts working as a mechano-sensor and other functions in the intestinal villi. Food and water intake deform villi and cause mechanical stress to the network of subepithelial fibroblasts (dark-blue cells). ATP is released from subepithelial fibroblasts by the mechanical stimulation and activates P2Y1 on surrounding cells as an autocrine mediator. The released ATP also activates the nerve endings of mucosal sensory neurons via P2X receptors. This represents a mechanosensing process in the villi and may contribute to the peristaltic reflex. Subepithelial fibroblast networks communicate with 
-SMA-negative lamina propria fibroblasts-like cells (gray cells) and they form three-dimensional networks. They closely contact capillary networks, sensory and motor neuronal networks, smooth muscles, and epithelium in the villi. Subepithelial fibroblasts communicate among these cell systems via released ATP and other humoral factors, such as TGF-ß, TNF-. From these views, we consider subepithelial fibroblasts work as barrier or sieve, mechano-sensor, mechanical frame, and signal transduction machinery in the villi. These functions are most likely locally and dynamically regulated in the villi by the rapid changes in cell-shape and mechano-sensitivity.
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