Fei Gao, Yujiro Hayashi, Siva Arumugam Saravanaperumal, Gabriella B Gajdos, Sabriya A Syed, Aditya V Bhagwate, Zhenqing Ye, Jian Zhong, Yuebo Zhang, Egan L Choi, Sergiy M Kvasha, Jagneet Kaur, Brooke D Paradise, Liang Cheng, Brandon W Simone, Alec M Wright, Todd A Kellogg, Michael L Kendrick, Travis J McKenzie, Zhifu Sun, Huihuang Yan, Chuanhe Yu, Adil E Bharucha, David R Linden, Jeong-Heon Lee, Tamas Ordog
BACKGROUND & AIMS: Although depletion of neuronal nitric oxide synthase (NOS1)-expressing neurons contributes to gastroparesis, stimulating nitrergic signaling is not an effective therapy. We investigated whether hypoxia-inducible factor 1α (HIF1A), which is activated by high O2 consumption in central neurons, is a Nos1 transcription factor in enteric neurons and whether stabilizing HIF1A reverses gastroparesis. METHODS: Mice with streptozotocin-induced diabetes, human and mouse tissues, NOS1+ mouse neuroblastoma cells, and isolated nitrergic neurons were studied...
August 18, 2023: Gastroenterology