Gong Xiang Liu1, Ying Xue Yang1, Jing Yan1, Tao Zhang1, Yu Pei Zou1, Xiao Li Huang2, Hua Tian Gan3. 1. Department of Geriatrics Medicine and Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China. 2. Department of Geriatrics Medicine and Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China. Electronic address: huangxiaoli@hotmail.com. 3. Department of Geriatrics Medicine and Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China. Electronic address: ganhuatian@hotmail.com.
Abstract
BACKGROUND: Intestinal inflammation is well known to cause gut dysmotility through the effects on the enteric nervous system. Glial-derived neurotrophic factor (GDNF) has been demonstrated to have anti-inflammatory effects and neuronal protective actions. The aim of this study was to investigate whether the GDNF could improve inflammation-induced gut dysmotility. METHODS: Recombinant adenoviral vectors encoding GDNF (Ad-GDNF) were administered intracolonically in experimental colitis induced by dextran sulfate sodium (DSS). The disease activity index (DAI) and histological score were measured. Colonic transit was measured by using phenol red and assessed with the geometric center. PGP 9.5 immunostaining was used to examine the number and distribution of enteric neurons. The expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and myeloperoxidase (MPO) activity were measured by ELISA assay. The expression of Akt, caspase-3, bcl-2 and PGP 9.5 was analyzed by western blot assay. RESULTS: A significant neuronal cell loss and a significant delay in colonic transit accompanied with the neuronal loss following inflammation were observed. GDNF prevented partially the loss of enteric neurons and ameliorated significantly experimental colitis and delayed colonic transit by, at least in part, down-regulation of TNF-α and IL-1β expression, decrease of infiltration of leukocytes, and inhibition of neuronal cell apoptosis. CONCLUSIONS: GDNF reduces inflammation and improves delayed colonic transit in DSS-induced colitis. GDNF may be a useful therapeutic agent for the treatment of gut dysmotility in patients with UC.
BACKGROUND: Intestinal inflammation is well known to cause gut dysmotility through the effects on the enteric nervous system. Glial-derived neurotrophic factor (GDNF) has been demonstrated to have anti-inflammatory effects and neuronal protective actions. The aim of this study was to investigate whether the GDNF could improve inflammation-induced gut dysmotility. METHODS: Recombinant adenoviral vectors encoding GDNF (Ad-GDNF) were administered intracolonically in experimental colitis induced by dextran sulfate sodium (DSS). The disease activity index (DAI) and histological score were measured. Colonic transit was measured by using phenol red and assessed with the geometric center. PGP 9.5 immunostaining was used to examine the number and distribution of enteric neurons. The expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and myeloperoxidase (MPO) activity were measured by ELISA assay. The expression of Akt, caspase-3, bcl-2 and PGP 9.5 was analyzed by western blot assay. RESULTS: A significant neuronal cell loss and a significant delay in colonic transit accompanied with the neuronal loss following inflammation were observed. GDNF prevented partially the loss of enteric neurons and ameliorated significantly experimental colitis and delayed colonic transit by, at least in part, down-regulation of TNF-α and IL-1β expression, decrease of infiltration of leukocytes, and inhibition of neuronal cell apoptosis. CONCLUSIONS:GDNF reduces inflammation and improves delayed colonic transit in DSS-induced colitis. GDNF may be a useful therapeutic agent for the treatment of gut dysmotility in patients with UC.