title: Lysophosphatidic acid increases SLC26A3 expression in inflamed intestine and reduces diarrheal severity in C57BL/6 mice with dextran-sodium-sulfate-induced colitis.
abstract: BACKGROUND
  Diarrhea is a common clinical feature of ulcerative colitis resulting from unbalanced intestinal fluid and salt absorption and secretion. The Cl(-)/HCO3(-) exchanger SLC26A3 is strongly expressed in the mid-distal colon and plays an essential role in colonic Cl(-) absorption and HCO3(-) secretion. Slc26a3 expression is up-regulated by lysophosphatidic acid (LPA) in vitro. Our study was designed to investigate the effects of LPA on SLC26A3 expression and the diarrheal phenotype in a mouse colitis model.
  
  
  METHODS
  Colitis was induced in C57BL/6 mice by adding 4% of dextran sodium sulfate (DSS) to the drinking water. The mice were assigned to LPA treatment DSS group, phosphate-buffered saline (PBS) treatment DSS group, DSS only group and untreated mice with a completely randomized design. Diarrhea severity was evaluated by measuring mice weight, disease activity index (DAI), stool water content and macroscopic evaluation of colonic damage. The effect of LPA treatment on Slc26a3 mRNA level and protein expression in the different groups of mice was investigated by quantitative PCR and Western blotting.
  
  
  RESULTS
  All mice treated with DSS lost weight, but the onset and severity of weight loss was attenuated in the LPA treatment DSS group. The increases in stool water content and the macroscopic inflammation score in LPA treatment DSS group were significantly lower compared to DSS control group or PBS treatment DSS group ((18.89±8.67)% vs. (28.97±6.95)% or (29.48±6.71)%, P = 0.049, P = 0.041, respectively and 2.67±0.81 vs. 4.5±0.83 or 4.5±0.54, P = 0.020, P = 0.006, respectively), as well as the increase in DAI (P = 0.004, P = 0.008, respectively). LPA enema resulted in higher Slc26a3 mRNA and protein expression levels compared to PBS-treated and untreated DSS colitis mice.
  
  
  CONCLUSIONS
  LPA increases Slc26a3 expression in the inflamed intestine and reduces diarrhea severity in DSS-induced colitis, suggesting LPA might be a therapeutic strategy in the treatment of colitis associated diarrhea.
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Hannover Medical School, 30625, Hannover, Germany.
authors.forename: Fang
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
authors.forename: Jiayi
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Lan
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
authors.forename: Junhua
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Hannover Medical School, 30625, Hannover, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Seidler
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital, Shihezi School of Medicine, Shihezi University, Shihezi, Xinjiang Uygur Autonomous Region 832008, China. Email: xueli_2006@163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. Email: datian@tjh.tjmu.edu.cn.
authors.forename: Dean
authors.initials: D
authors.lastname: Tian
mesh_terms: D000818:Animals; D017920:Antiporters / Q000235:genetics / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D003106:Colon / Q000276:immunology / Q000378:metabolism; D016264:Dextran Sulfate / Q000494:pharmacology*; D003911:Dextrans / Q000494:pharmacology*; D003967:Diarrhea / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D015151:Immunoblotting; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects*; D008246:Lysophospholipids / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D000076988:Sulfate Transporters
chemical_list: D017920:Antiporters; D003911:Dextrans; D008246:Lysophospholipids; C489860:Slc26a3 protein, mouse; D000076988:Sulfate Transporters; D016264:Dextran Sulfate; C032881:lysophosphatidic acid