Neuropeptide Y inhibits biliary hyperplasia of cholestatic rats by paracrine and autocrine mechanisms
| Autor: | Gabriel Frampton, Fanyin Meng, Romina Mancinelli, Paolo Onori, Kelly McDaniel, Julie Venter, Dinorah Leyva-Illades, Gianfranco Alpini, Matthew A. Quinn, Shannon Glaser, Antonio Franchitto, Eugenio Gaudio, Hae Yong Pae, Heather Francis, Sharon DeMorrow |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Physiology proliferation Paracrine Communication Biology Autocrine Communication digestive system neurotransmitters Cell Line Paracrine signalling Proliferating Cell Nuclear Antigen Physiology (medical) Internal medicine mental disorders medicine Animals Homeostasis Neuropeptide Y RNA Messenger Autocrine signalling Receptor Cell Proliferation Cholestasis Hyperplasia Hepatology biliary epithelium Biliary hyperplasia Gastroenterology Neuropeptide Y receptor Antibodies Neutralizing Rats Inbred F344 humanities Rats Receptors Neuropeptide Y Liver and Biliary Tract Bile Ducts Intrahepatic Endocrinology cell cycle Signal transduction Signal Transduction |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 305:G250-G257 |
| ISSN: | 1522-1547 0193-1857 |
| DOI: | 10.1152/ajpgi.00140.2013 |
| Popis: | Neuropeptide Y (NPY) exerts its functions through six subtypes of receptors (Y1–Y6). Biliary homeostasis is regulated by several factors through autocrine/paracrine signaling. NPY inhibits cholangiocarcinoma growth; however, no information exists regarding the autocrine/paracrine role of NPY on biliary hyperplasia during cholestasis. The aims of this study were to determine: 1) the expression of NPY and Y1–Y5 in cholangiocytes and 2) the paracrine/autocrine effects of NPY on cholangiocyte proliferation. Normal or bile duct ligation (BDL) rats were treated with NPY, neutralizing anti-NPY antibody, or vehicle for 7 days. NPY and NPY receptor (NPYR) expression was assessed in liver sections and isolated cholangiocytes. NPY secretion was assessed in serum and bile from normal and BDL rats, as well as supernatants from normal and BDL cholangiocytes and normal rat cholangiocyte cell line [intrahepatic normal cholangiocyte culture (NRICC)]. We evaluated intrahepatic bile ductal mass (IBDM) in liver sections and proliferation in cholangiocytes. With the use of NRICC, the effects of NPY or anti-NPY antibody on cholangiocyte proliferation were determined. The expression of NPY and all NPYR were increased after BDL. NPY levels were lower in serum and cholangiocyte supernatant from BDL compared with normal rats. NPY secretion from NRICC was detected at both the basolateral and apical domains. Chronic NPY treatment decreased proliferating cellular nuclear antigen (PCNA) expression and IBDM in BDL rats. Administration of anti-NPY antibody to BDL rats increased cholangiocyte proliferation and IBDM. NPY treatment of NRICC decreased PCNA expression and increased the cell cycle arrest, whereas treatment with anti-NPY antibody increased proliferation. Therapies targeting NPY-mediated signaling may prove beneficial for the treatment of cholangiopathies. |
| Databáze: | OpenAIRE |
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