Knockout of histidine decarboxylase decreases bile duct ligation-induced biliary hyperplasia via downregulation of the histidine decarboxylase/VEGF axis through PKA-ERK1/2 signaling

• DOI: 10.1152/ajpgi.00188.2014
• Publication Date: 2014-08-29T07:39:20Z
• Authors: Allyson Graf; Fanyin Meng; Laura Hargrove; Lindsey Kennedy; Yuyan Han; Taylor Francis; Kyle Hodges; Yoshiyuki Ueno; Quy Nguyen; John F. Greene; Heather Francis
• Keywords: Histidine decarboxylase; Cholangiocyte

Histidine is converted to histamine by histidine decarboxylase (HDC). We have shown that cholangiocytes 1) express HDC, 2) secrete histamine, and 3) proliferate after treatment via ERK1/2 signaling. In bile duct-ligated (BDL) rodents, there enhanced biliary hyperplasia, HDC expression, secretion. This studied aimed demonstrate knockdown of inhibits proliferation downregulation PKA/ERK1/2 HDC(-/-) mice matching wild-type (WT) were subjected sham or BDL. After 1 wk, serum, liver blocks, collected. Immunohistochemistry was performed for hematoxylin eosin, intrahepatic duct mass (IBDM) cytokeratin-19, expression. measured serum cholangiocyte levels enzyme immunoassay. total cholangiocytes, we studied: VEGF/HIF-1α expression PCNA protein vitro, stably transfected with shRNA-HDC plasmids (or control). transfection evaluated pPKA, pERK1/2, immunoblots MTT assay. BDL mice, decreased IBDM, PCNA, VEGF, compared WT mice. Histamine in HDC(-/-). livers void necrosis inflammation WT. (increased BDL) lower cholangiocytes. control. conclusion, loss decreases BDL-induced Our data suggest a key regulator proliferation.