title: Evaluation of p38 MAPK pathway as a molecular signature in ulcerative colitis.
abstract: Early diagnosis and treatment of ulcerative colitis (UC) is clinically challenging. To overcome this problem, we explored the interrelated multiplex signaling pathway to identify molecular signatures in UC by using integrated strategy in proteomics. Intestinal mucosa of 12 UC cases and 12 normal controls underwent comparative proteomic analysis. A total of 26 unique differential proteins were identified, including 12 up-regulated and 14 down-regulated in UC group. A differential protein cluster, consisting of 11 proteins involved in p38 mitogen-activated protein kinase (MAPK) pathway, was deduced and validated by Western blot. Furthermore, three proteins elicited from the protein cluster, phosphorylated p38, MAWBP and galectin-3, as a molecular signature, were analyzed by immunohistochemistry on 118 UC and normal samples. Increased expression of P-p38 and down-regulated MAWBP and/or galectin-3 were detected in UC compared to normal samples (p < 0.001). This signature correlated with disease progression of UC (p < 0.01), and classified UC risk with high sensitivity (94.83 ± 2.91%) and specificity (98.33 ± 1.65%). In addition, P38 MAPK pathway modulated the expression of the protein clusters in macrophage cell line as evidenced by the alteration with specific inhibitor SB203580. These results indicate that molecular signature of P38 MAPK pathway might be a potential biomarker for evaluating UC risk.
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xinmei
authors.initials: X
authors.lastname: Zhao
authors.forename: Bin
authors.initials: B
authors.lastname: Kang
authors.forename: Chaolan
authors.initials: C
authors.lastname: Lu
authors.forename: Siqi
authors.initials: S
authors.lastname: Liu
authors.forename: Huanjing
authors.initials: H
authors.lastname: Wang
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yang
authors.forename: Ye
authors.initials: Y
authors.lastname: Chen
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Youyong
authors.initials: Y
authors.lastname: Lu
authors.forename: Fachao
authors.initials: F
authors.lastname: Zhi
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000378:metabolism*; D037502:Galectin 3 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D011725:Pyridines / Q000494:pharmacology; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D037502:Galectin 3; D007093:Imidazoles; C434327:PBLD protein, human; D011506:Proteins; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580