title: Runx1-deficient afferents impair visceral nociception, exacerbating dextran sodium sulfate-induced colitis.
abstract: Colitis is a group of inflammatory and auto-immune disorders that affect the tissue lining of the gastrointestinal (GI) system. Studies of chemically-induced animal models of colitis have indicated that nociceptive afferents or neuropeptides have differing effects on GI inflammation. However, the molecular mechanisms involved in visceral pain and the role of visceral sensory afferents involved in the modulation of colitis remains unclear. A previous study demonstrated that Runx1, a Runt domain transcription factor, is restricted to nociceptors. In these neurons, Runx1 regulates the expression of numerous ion channels and receptors, controlling the lamina-specific innervation patterns of nociceptive afferents in the spinal cord. Moreover, mice that lack Runx1 exhibit specific defects in thermal and neuropathic pain. To examine the function of Runx1 in visceral nociception, we employed double-transgenic mice (WntCre: Runx1(F/F)), in which the expression of Runx1 was specifically disrupted in the sensory neurons. To determine the role of Runx1 in visceral pain sensation, the WntCre: Runx1(F/F) mice and their control littermates (Runx1(F/F)) were treated using dextran sodium sulfate (DSS) to induce colitis. The results indicated that disrupted Runx1 in the sensory afferents resulted in: (1) impairment of the visceral pain sensation in murine DSS-induced colitis; (2) exacerbating the phenotypes in murine DSS-induced colitis; (3) a differential effect on the production of pro- and anti-inflammatory cytokines in the colon tissues isolated from mice treated using DSS and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis; and (4) alteration of the distribution of lymphocytes and mast cells in mucosa. These results show that the function of Runx1 in sensory afferents is vital for modulating visceral pain and the neuro-immune axis.
authors.affiliation: Department of Pediatrics, Cathay General Hospital, Taipei, Taiwan.
authors.forename: Shih-Ping
authors.initials: SP
authors.lastname: Hung
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan.
authors.forename: Ming-Jen
authors.initials: MJ
authors.lastname: Sheu
authors.affiliation: School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Ming Chieh
authors.initials: MC
authors.lastname: Ma
authors.affiliation: Liver Unit, Cathay General Hospital, Taipei, Taiwan.
authors.forename: Jui-Ting
authors.initials: JT
authors.lastname: Hu
authors.affiliation: Graduate Institute of Basic Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Ya-Yun
authors.initials: YY
authors.lastname: Sun
authors.affiliation: Department of Pathology, Shin Kong Memorial Hospital, Taipei, Taiwan.
authors.forename: Chin-Cheng
authors.initials: CC
authors.lastname: Lee
authors.affiliation: Department of Surgery, Cheng Ching General Hospital, Chung-Kang Branch, Taichung, Taiwan.
authors.forename: Yuan-Chiang
authors.initials: YC
authors.lastname: Chung
authors.affiliation: School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Tsai
authors.affiliation: School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Jing-Yuan
authors.initials: JY
authors.lastname: Wang
authors.affiliation: School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan. Electronic address: 059271@mail.fju.edu.tw.
authors.forename: Chih-Li
authors.initials: CL
authors.lastname: Chen
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D050676:Core Binding Factor Alpha 2 Subunit / Q000172:deficiency / Q000502:physiology*; D016264:Dextran Sulfate / Q000494:pharmacology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000502:physiology*; D059225:Nociception / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011984:Sensory Receptor Cells / Q000502:physiology; D059265:Visceral Pain / Q000209:etiology / Q000503:physiopathology*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C493726:Runx1 protein, mouse; D016264:Dextran Sulfate
keywords: Colitis; Dextran sodium sulfate (DSS); Runx1; Visceral nociception