Up-Regulated the Expression of MRP3 and MRP4 through FGF19-ERK Pathway to Protect Hepatocytes Under Cholestasis

Yu Wenjing¹, Shi Pan¹, Pan Qiong², Chai jin², Song Shuliang¹*

(¹China Marine College, Shandong University at Weihai, Weihai 264209, China; ²Cholestatic Liver Diseases Center and Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China)

Abstract:

In this study, qRT-PCR and Western blot were used to detect the change expression of autocrine fibroblast growth factor 19 (FGF19), amultidrug resistance-associated protein 3 (MRP3) and multidrug resistance-associated protein 4 (MRP4), when the HepG2 cells were treated with FGF19. The results showed that the expression of MRP3 and MRP4 both in mRNA level and protein level were up-regulated in a concentration-and time-dependent manner. It was further confirmed by Western blot that the protein level of phosphorylated extracellular signal related kinase (p-ERK) was increased, when treated the HepG2 cells with FGF19. When the HepG2 cells were pretreated with PD98059, specific small molecule inhibitor of ERK signaling pathway, the expression of MRP3 and MRP4 was decreased, comparing to control group without PD98059. The results indicated that FGF19 specifically mediated up-regulation of MRP3 and MRP4 by regulating ERK signaling pathway, and enhanced hepatoprotection by increasing bile acid excretion under cholestasis conditions.

CSTR: 32200.14.cjcb.2019.08.0013