Hepatic fibrogenesis requires sympathetic neurotransmitters

Oben, J. A.; Roskams, T.; Yang, S.; Lin, H.; Sinelli, N.; Torbenson, M.; Smedh, U.; Moran, T. H.; Li, Z.; Huang, J.; Thomas, S. A.; Diehl, A. M.
March 2004
Gut;Mar2004, Vol. 53 Issue 3, p438
Academic Journal
Background and aims: Hepatic stellate cells (HSC) are activated by liver injury to become proliferative fibrogenic myofibroblasts. This process may be regulated by the sympathetic nervous system (SNS) but the mechanisms involved are unclear. Methods: We studied cultured HSC and intact mice with liver injury to test the hypothesis that HSC respond to and produce SNS neurotransmitters to promote fibrogenesis. Results: HSC expressed odrenoceptors, catecholamine biosynthetic enzymes, released norepinephrine (NE), and were growth inhibited by α- and β-adrenoceptor antagonists. HSC from dopamine β-hydroxylose deficient (Dbh-/-) mice, which cannot make NE, grew poorly in culture and were rescued by NE. Inhibitor studies demonstrated that this effect was mediated via G protein coupled adrenoceptors, mitogen activated kinases, and phosphatidylinositol 3-kinase. Injury related fibrogenic responses were inhibited in Dbh-/- mice, as evidenced by reduced hepatic accumulation of α-smooth muscle actin+ve HSC and decreased induction of transforming growth factor β1 (TGF-β1) and collagen. Treatment with isoprenaline rescued HSC activation. HSC were also reduced in leptin deficient ob/ob mice which have reduced NE levels and ore resistant to hepatic fibrosis. Treating ob/ob mice with NE induced HSC proliferation, upregulated hepatic TGF-β1 and collagen, and increased liver fibrosis. Conclusions: HSC are hepatic neuroglia that produce and respond to SNS neurotransmitters to promote hepatic fibrosis.


Related Articles

  • enzymes (Major drug group).  // Royal Society of Medicine: Medicines;2002, p228 

    The article presents information on enzymes. They are proteins that play an essential part in the body's processes by acting as catalysts in specific, necessary biochemical reactions. Their physiological functions range from digestion of food within the digestive tract, formation of hormones and...

  • Is there a role of hepatic enzymes in the management of penetrating hepatic injuries? Pallett, J. R.; Gibbon, A.; Keep, J. W. // Scandinavian Journal of Trauma, Resuscitation & Emergency Medici;2013, Vol. 21 Issue Suppl 1, p1 

    An abstract of the article "Is there a role of hepatic enzymes in the management of penetrating hepatic injuries?," by J. R. Pallett and colleagues is presented.

  • PLASMA MEMBRANES IN ACUTE LIVER INJURY. BIOCHEMICAL CHANGES INDUCED BY CARBON TETRACHLORIDE. Le Page, R. N.; Dorling, P. R. // Australian Journal of Experimental Biology & Medical Science;Aug1971, Vol. 49 Issue 4, p345 

    The article presents a study of the effects of toxic liver injury in liver-cell plasma membrane. Membrane permeability of injured liver cells appears to be altered, such that intracellular concentrations of ions are altered. In the present studies plasma membranes isolated from liver of control...

  • COMBINED EXPOSURE TO M-XYLENE AND ETHANOL:OXIDATIVE STRESS IN THE RAT LIVER. Jajte, Jolanta; Stetkiewicz, Jan; Wronska-Nofer, Teresa // International Journal of Occupational Medicine & Environmental H;Oct2003, Vol. 16 Issue 4, p345 

    Objectives: Ethanol may be a significant combined factor in human solvent toxicity. Lipid peroxidation has been suggested to be an important contributing mechanism involved in experimental alcohol-induced liver injury. The aim of the study was to investigate whether a short-term ethanol...

  • Serum Liver Enzyme Pattern in Birth Asphyxia Associated Liver Injury. Chhavi, Nanda; Zutshi, Kiran; Singh, Niranjan Kumar; Awasthi, Ashish; Goel, Amit // Pediatric Gastroenterology, Hepatology & Nutrition;Sep2014, Vol. 17 Issue 3, p162 

    Purpose: To study temporal pattern of serum liver enzymes levels in newborns with hepatic injury associated with birth asphyxia (BA). Methods: Singleton term newborns with BA and =72 hours of age admitted to neonatal intensive care unit were prospectively enrolled. Term newborns with...

  • Risk factors for elevated liver enzymes during refeeding of severely malnourished patients with eating disorders: a retrospective cohort study. Miho Imaeda; Satoshi Tanaka; Hiroshige Fujishiro; Saki Kato; Masatoshi Ishigami; Naoko Kawano; Hiroto Katayama; Kunihiro Kohmura; Masahiko Ando; Kazuo Nishioka; Norio Ozaki // Journal of Eating Disorders;12/7/2016, Vol. 4, p1 

    Background: There are few previous reports regarding the cause and evolution of liver injury in patients with anorexia nervosa (AN) during the refeeding process, and its management remains controversial. This study aimed to determine the risk factors for elevated liver enzymes during refeeding...

  • Mast Cell Density, Hepatic Stellate Cell Activation and TGF-� 1 Transcripts in the Aging Sprague-Dawley Rat During Early Acute Liver Injury. Grizzi, F.; Franceschini, B.; Gagliano, N.; Moscheni, C.; Annoni, G.; Vergani, C.; Hermonat, P. L.; Chiriva-Internati, M.; Dioguardi, N. // Toxicologic Pathology;Mar/Apr2003, Vol. 31 Issue 2, p173 

    Mast cells (MCs) have been indicated as a source of various inflammatory cytokines, chemokines and growth factors. This study evaluates liver tissue MC density as a quantitative marker of acute liver inflammation in 2- and 19-month old rats treated with carbon tetrachloride (CCl 4 ) to assess...

  • Origin of myofibroblasts in liver fibrosis. Brenner, David A.; Kisseleva, Tatiana; Scholten, David; Tong Han Paik; Iwaisako, Keiko; Inokuchi, Sayaka; Schnabl, Bernd; Seki, Ekihiro; de Minicis, Samuele; Oesterreicher, Christoph; Taura, Kojiro // Fibrogenesis & Tissue Repair;2012, Vol. 5 Issue Suppl 1, p1 

    Most chronic liver diseases of all etiologies result in progressive liver fibrosis. Myofibroblasts produce the extracellular matrix, including type I collagen, which constitutes the fibrous scar in liver fibrosis. Normal liver has little type I collagen and no detectable myofibroblasts, but...

  • Neighborhood watch orchestrates liver regeneration. Diehl, Anna Mae // Nature Medicine;Apr2012, Vol. 18 Issue 4, p497 

    The article focuses on the study by Boulter and colleagues regarding the effect of liver injury to the progenitors niche to direct progenitor fate during regeneration. It says that the bipotent progenitors localize on the canals of Herring, which are delianated by matrix-producing cells that...


Read the Article


Sign out of this library

Other Topics