title: Liver 5-HT7 receptors: A novel regulator target of fibrosis and inflammation-induced chronic liver injury in vivo and in vitro.
abstract: OBJECTIVE
  Hepatocellular cancer (HCC) is the sixth most common cancer and liver fibrosis is strongly associated with HCC. Treatment options are limited, and preventive strategies should be developed. An important step in the beginning of liver fibrosis is a strong inflammatory response. 5-HT7 is the last recognized member of the serotonin receptor family and is expressed in both central nerve system and peripheral system and have a lot of functions like learning, memory, smooth muscular relaxation, in the control of circadian rhythms and thermoregulation, pain and migraine, schizophrenia, anxiety, cognitive disturbances, and even inflammation.
  
  
  METHODS
  We therefore examined the biochemical, histopathological and molecular effects of the 5-HT7 receptor agonist and antagonist on inflammatory liver fibrogenesis in animal models of progressive cirrhosis: a mouse model induced by carbon tetrachloride (CCl4) and in Hep3b cells.
  
  
  RESULTS
  5-HT7 expression was observed in the liver in vivo and in vitro in CCl4-induced damage. 5-HT7 receptor agonist but not the antagonist reduced liver markers in mice and in Hep3b cells in carbon tetrachloride (CCl4) induced damage. 5-HT7 agonist, but not antagonist, protected liver tissue from oxidative stress in fibrosis. 5-HT7 agonist but not antagonist induces anti-inflammatory, anti-fibrinotic and anti-cytokine features in liver fibrosis in vivo and in vitro.
  
  
  CONCLUSIONS
  5-HT7 receptors have modulatory function and are an up-and-coming pharmacological target in the inflammatory fibrotic process. 5-HT7 receptor agonist LP-44 showed significant hepatoprotective effects against liver fibrosis, and LP-44 might become a useful therapeutic target for chronic liver inflammation and fibrosis.
authors.affiliation: Ataturk University, Faculty of Pharmacy, Department of Pharmacology, 25240 Erzurum, Turkey.
authors.forename: Beyzagul
authors.initials: B
authors.lastname: Polat
authors.affiliation: Ataturk University, Faculty of Medicine, Department of Pharmacology, 25240 Erzurum, Turkey. Electronic address: hzekai@gmail.com.
authors.forename: Zekai
authors.initials: Z
authors.lastname: Halici
authors.affiliation: Ataturk University, Faculty of Medicine, Department of Pharmacology, 25240 Erzurum, Turkey.
authors.forename: Elif
authors.initials: E
authors.lastname: Cadirci
authors.affiliation: Ataturk University, Faculty of Veterinary, Department of Pharmacology and Toxicology, 25240 Erzurum, Turkey.
authors.forename: Emre
authors.initials: E
authors.lastname: Karakus
authors.affiliation: Ataturk University, Faculty of Pharmacy, Department of Biochemistry, 25240 Erzurum, Turkey.
authors.forename: Yasin
authors.initials: Y
authors.lastname: Bayir
authors.affiliation: Ataturk University, Faculty of Medicine, Department of Pharmacology, 25240 Erzurum, Turkey.
authors.forename: Abdulmecit
authors.initials: A
authors.lastname: Albayrak
authors.affiliation: Ataturk University, Faculty of Medicine, Department of Embryology and Histology, 25240 Erzurum, Turkey.
authors.forename: Deniz
authors.initials: D
authors.lastname: Unal
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000276:immunology*; D002460:Cell Line; D005355:Fibrosis; D006801:Humans; D007249:Inflammation; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000276:immunology*; D055370:Lung Injury / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D010636:Phenols; D011985:Receptors, Serotonin; C404922:SB 269970; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; C104425:serotonin 7 receptor; D002251:Carbon Tetrachloride
keywords: CCl4; Fibrosis; Inflammation; Liver injury; Serotonin