C.S. Justo-Jaume1, C.I. Moneme1, O.S. Jung1, M.F. Sobstel1, P. Obidike1, Y. Zhang1, L. Cheng1 1University Of Virginia, Surgery, Charlottesville, VA, USA
Introduction: The Piezo family of mechanosensitive ion channels has recently been discovered to play an important role in the function of several visceral organs, including the gastrointestinal (GI) system. We have previously found that Piezo1 activation/inhibition affects the growth of enteric neurons and that Piezo1 expression in the GI tract is diminished in Hirschsprung disease. However, the role of Piezo1 in GI motility has not yet been established. We hypothesize that Piezo1 loss-of-function in intestinal smooth muscle will lead to GI dysmotility.
Methods: An inducible smooth muscle-specific Piezo1 knockout mouse (Piezo1 fl/fl MYH11 CreERT) was generated and Cre+/Cre- adult mice were treated with tamoxifen to induce the conditional deletion of Piezo1 in smooth muscle cells. To confirm the absence of Piezo1 expression in the intestinal smooth muscle in Cre+ mice, the small intestine and colon were isolated, cryosectioned, and immunohistochemistry was performed for Piezo1 and alpha-smooth muscle actin. Total GI transit time, number of pellets per hour, stool weight, stool water content, and colon length were then compared between Cre+ and Cre- littermates (n=3 each group).
Results: There was no significant difference in GI motility between smooth-muscle specific Piezo1 knockout mice and Cre- controls as measured by several functional assays including total GI transit time (4.5 ± 1.3 vs. 4.5 ± 2.2 hours), stool weight (25.4 ± 2.3 vs. 36.8 ± 14.1 grams/pellet), stool water weight (29.4 ± 9.0% vs. 47.1 ± 29.1%), pellets per hour (1.7 ± 1.2 vs. 1.3 ± 1.2), and colon length (8.0 ± 1.0 vs. 7.2 ± 1.0 cm) respectively.
Conclusion: This is the first study to examine the role of Piezo1 in intestinal smooth muscle. No difference in GI motility was seen in our small sample of smooth-muscle-specific Piezo1 knockout mice. Further study is needed to understand the relationship between Piezo1 and GI motility.