title: Intestinal Metrnl released into the gut lumen acts as a local regulator for gut antimicrobial peptides.
abstract: OBJECTIVE
  Metrnl is a novel secreted protein, but its physiological roles remain elusive. In this study, we investigated the tissue expression pattern of Metrnl in humans and explored its possible physiological role in the tissues with most highly expressed levels.
  
  
  METHODS
  A human tissue microarray containing 19 types of tissues from 69 donors was used to examine the tissue expression pattern of Metrnl, and the expression pattern was further verified in fresh human and mouse tissues. Intestinal epithelial cell-specific Metrnl knockout mice were generated, which were used to analyze the physiological roles of Metrnl.
  
  
  RESULTS
  Metrnl was the most highly expressed in the human gastrointestinal tract, and was specifically expressed in the intestinal epithelium. Consistent with this, Metrnl mRNA was also most highly expressed in the mouse gastrointestinal tract among the 14 types of tissues tested. In the intestinal epithelial cell-specific Metrnl knockout mice, the Metrnl levels in the gut fluid were significantly reduced, whereas the Metrnl serum levels showed a trend towards a reduction, but this change was not statistically significant. This cell-specific deletion of Metrnl did not affect body weight, food intake, blood glucose, colon length and histology, intestinal permeability, mucus content or mucin 2 expression under physiological conditions, but statistically decreased the expression of antimicrobial peptides, such as regenerating islet-derived 3 gamma (Reg3g) and lactotransferrin.
  
  
  CONCLUSIONS
  Metrnl is highly expressed in the intestinal epithelial cells of humans and mice, which mainly contributes to the local gut Metrnl levels and affects the serum Metrnl level to a lesser extent. Metrnl plays a role in maintaining gut antimicrobial peptides.
authors.affiliation: Department of Pharmacology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Mao-Bing
authors.initials: MB
authors.lastname: Fan
authors.affiliation: Department of Pharmacology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Sai-Long
authors.initials: SL
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Department of Pharmacology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Si-Li
authors.initials: SL
authors.lastname: Zheng
authors.affiliation: Department of Pharmacology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Pharmacology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Chao-Yu
authors.initials: CY
authors.lastname: Miao
mesh_terms: D054392:Adipokines / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D003106:Colon / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007781:Lactoferrin / Q000378:metabolism; D008297:Male; D018345:Mice, Knockout; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D054392:Adipokines; D023181:Antimicrobial Cationic Peptides; C000593412:Metrnl protein, human; D009414:Nerve Growth Factors; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C490253:Reg3b protein, mouse; C490255:Reg3g protein, mouse; C076498:Saa3 protein, mouse; D000685:Serum Amyloid A Protein; C570859:cometin protein, mouse; D007781:Lactoferrin