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Merck
CN
  • Gonadotropin-releasing hormone stimulates biliary proliferation by paracrine/autocrine mechanisms.

Gonadotropin-releasing hormone stimulates biliary proliferation by paracrine/autocrine mechanisms.

The American journal of pathology (2015-03-22)
Debolina Ray, Yuyan Han, Antonio Franchitto, Sharon DeMorrow, Fanyin Meng, Julie Venter, Matthew McMillin, Lindsey Kennedy, Heather Francis, Paolo Onori, Romina Mancinelli, Eugenio Gaudio, Gianfranco Alpini, Shannon S Glaser
摘要

During cholestatic liver disease, there is dysregulation in the balance between biliary growth and loss in bile duct-ligated (BDL) rats modulated by neuroendocrine peptides via autocrine/paracrine pathways. Gonadotropin-releasing hormone (GnRH) is a trophic peptide hormone that modulates reproductive function and proliferation in many cell types. We evaluated the autocrine role of GnRH in the regulation of cholangiocyte proliferation. The expression of GnRH receptors was assessed in a normal mouse cholangiocyte cell line (NMC), sham, and BDL rats. The effect of GnRH administration was evaluated in normal rats and in NMC. GnRH-induced biliary proliferation was evaluated by changes in intrahepatic bile duct mass and the expression of proliferation and function markers. The expression and secretion of GnRH in NMC and isolated cholangiocytes was assessed. GnRH receptor subtypes GnRHR1 and GnRHR2 were expressed in cholangiocytes. Treatment with GnRH increased intrahepatic bile duct mass as well as proliferation and function markers in cholangiocytes. Transient knockdown and pharmacologic inhibition of GnRHR1 in NMC decreased proliferation. BDL cholangiocytes had increased expression of GnRH compared with normal rats, accompanied by increased GnRH secretion. In vivo and in vitro knockdown of GnRH decreased intrahepatic bile duct mass/cholangiocyte proliferation and fibrosis. GnRH secreted by cholangiocytes promotes biliary proliferation via an autocrine pathway. Disruption of GnRH/GnRHR signaling may be important for the management of cholestatic liver diseases.

材料
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品牌
产品描述

Sigma-Aldrich
腺苷-3′,5′-环单磷酸, ≥98.5% (HPLC), powder
Sigma-Aldrich
DL-甘油醛-3-磷酸 溶液, 45-55 mg/mL in H2O
Sigma-Aldrich
腺苷-3′,5′-环单磷酸 三羟甲基氨基甲烷盐, ≥97% (HPLC), powder