Matrine induces the hepatic differentiation of WB-F344 rat hepatic progenitor cells and inhibits Jagged 1/HES1 signaling

Yang,Zhiyun; Wang,Li; Wang,Xianbo

doi:10.3892/mmr.2016.5668

Matrine induces the hepatic differentiation of WB-F344 rat hepatic progenitor cells and inhibits Jagged 1/HES1 signaling

Authors:
- Zhiyun Yang
- Li Wang
- Xianbo Wang
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Affiliations: Department of Traditional Chinese Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China
Published online on: August 24, 2016 https://doi.org/10.3892/mmr.2016.5668
Pages: 3841-3847

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Abstract

Matrine is a Chinese medicine, which is widely utilized for the attenuation of liver injuries and promotion of liver regeneration. It was previously observed that the in vivo administration of matrine promoted oval cell‑mediated liver regeneration in a rat model, suggesting that this compound may affect the differentiation of hepatic progenitor cells. The present study aimed to determine the mechanisms underlying this observation and to investigate the effect of matrine on the differentiation of the WB‑F344 rat hepatic progenitor cell line. Matrine was administered to rats, and rat serum was collected. WB‑F344 cells were cultured in the presence or absence of the rat serum for 24‑72 h, and the effects on cell viability and proliferation were assessed using acridine orange/propidium iodide staining and a 3‑(4,5‑dimethylthiazol‑2‑yl) ‑2,5‑diphenyltetrazolium bromide assay. The expression of albumin (ALB, a hepatocyte marker) and the notch signaling pathway ligand, Jagged 1, were assessed using immunohistochemistry and western blotting, and the mRNA transcription of ALB, Jagged 1 and hairy and enhancer of split‑1 (HES1, another notch signaling ligand) were measured using reverse transcription‑polymerase chain reaction analysis. The results showed that proliferation of the WB‑F344 cells was inhibited by matrine serum in a concentration‑ and time‑dependent manner. Matrine serum downregulated Jagged 1 and HES1, and upregulated ALB, indicating the induction of WB‑F344 cell differentiation. The effects of matrine serum were reversed by supplementing the culture medium with 0.1 mol/l parathyroid hormone, a Notch signaling pathway activator. In conclusion, matrine induced hepatic differentiation of the hepatic progenitor cells, likely by inhibiting the Jagged 1/HES1 signaling pathway.

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1	Zhu Y, Miao Z, Gong L and Chen W: Transplantation of mesenchymal stem cells expressing TIMP-1-shRNA improves hepatic fibrosis in CCl₄-treated rats. Int J Clin Exp Pathol. 8:8912–8920. 2015.
2	Tessier S, Karczewski P, Krause EG, Pansard Y, Acar C, Lang-Lazdunski M, Mercadier JJ and Hatem SN: Regulation of the transient outward K(+) current by Ca(2+)/calmodulin-dependent protein kinases II in human atrial myocytes. Circ Res. 85:810–819. 1999. View Article : Google Scholar : PubMed/NCBI
3	Bodart V, Bouchard JF, McNicoll N, Escher E, Carrière P, Ghigo E, Sejlitz T, Sirois MG, Lamontagne D and Ong H: Identification and characterization of a new growth hormone-releasing peptide receptor in the heart. Circ Res. 85:796–802. 1999. View Article : Google Scholar : PubMed/NCBI
4	Knight B, Akhurst B, Matthews VB, Ruddell RG, Ramm GA, Abraham LJ, Olynyk JK and Yeoh GC: Attenuated liver progenitor (oval) cell and fibrogenic responses to the choline deficient, ethionine supplemented diet in the BALB/c inbred strain of mice. J Hepatol. 46:134–141. 2007. View Article : Google Scholar
5	Roskams TA, Theise ND, Balabaud C, Bhagat G, Bhathal PS, Bioulac-Sage P, Brunt EM, Crawford JM, Crosby HA, Desmet V, et al: Nomenclature of the finer branches of the biliary tree: Canals, ductules, and ductular reactions in human livers. Hepatology. 39:1739–1745. 2004. View Article : Google Scholar : PubMed/NCBI
6	Duncan AW, Dorrell C and Grompe M: Stem cells and liver regeneration. Gastroenterology. 137:466–481. 2009. View Article : Google Scholar : PubMed/NCBI
7	Newsome PN, Hussain MA and Theise ND: Hepatic oval cells: Helping redefine a paradigm in stem cell biology. Curr Top Dev Biol. 61:1–28. 2004. View Article : Google Scholar : PubMed/NCBI
8	Tanimizu N, Tsujimura T, Takahide K, Kodama T, Nakamura K and Miyajima A: Expression of Dlk/Pref-1 defines a subpopulation in the oval cell compartment of rat liver. Gene Expr Patterns. 5:209–218. 2004. View Article : Google Scholar : PubMed/NCBI
9	Yano Y, Hayashi Y, Teramoto T, Nakaji M, Nagy P, Ninomiya T, Wada A, Hirai M, Kim SR, Seo Y, et al: Apoptotic pathway related to oval cell proliferation. J Gastroenterol Hepatol. 19:866–872. 2004. View Article : Google Scholar : PubMed/NCBI
10	Lee TY, Chang HH, Lo WC and Lin HC: Alleviation of hepatic oxidative stress by Chinese herbal medicine Yin-Chen-Hao-Tang in obese mice with steatosis. Int J Mol Med. 25:837–844. 2010. View Article : Google Scholar : PubMed/NCBI
11	Liu T, Song Y, Chen H, Pan S and Sun X: Matrine inhibits proliferation and induces apoptosis of pancreatic cancer cells in vitro and in vivo. Biol Pharm Bull. 33:1740–1745. 2010. View Article : Google Scholar : PubMed/NCBI
12	Gao HY, Li GY, Lou MM, Li XY, Wei XY and Wang JH: Hepatoprotective effect of Matrine salvianolic acid B salt on carbon tetrachloride-induced hepatic fibrosis. J Inflamm (Lond). 9:162012. View Article : Google Scholar
13	Zhang F, Wang X, Tong L, Qiao H, Li X, You L, Jiang H and Sun X: Matrine attenuates endotoxin-induced acute liver injury after hepatic ischemia/reperfusion in rats. Surg Today. 41:1075–1084. 2011. View Article : Google Scholar : PubMed/NCBI
14	Yang ZY, Wang L, Hou YX and Wang XB: Effects of matrine on oval cell-mediated liver regeneration and expression of RBP-Jκ and HES1. Mol Med Rep. 7:1533–1538. 2013.PubMed/NCBI
15	Jubb AM, Browning L, Campo L, Turley H, Steers G, Thurston G, Harris AL and Ansorge O: Expression of vascular Notch ligands Delta-like 4 and Jagged-1 in glioblastoma. Histopathology. 60:740–747. 2012. View Article : Google Scholar : PubMed/NCBI
16	Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC, Martin RP, Schipani E, Divieti P, Bringhurst FR, et al: Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 425:841–846. 2003. View Article : Google Scholar : PubMed/NCBI
17	Ke Z, Mao X, Li S, Wang R, Wang L and Zhao G: Dynamic expression characteristics of Notch signal in bone marrow-derived mesenchymal stem cells during the process of differentiation into hepatocytes. Tissue Cell. 45:95–100. 2013. View Article : Google Scholar
18	Zhang JQ, Li YM, Liu T, He WT, Chen YT, Chen XH, Li X, Zhou WC, Yi JF and Ren ZJ: Antitumor effect of matrine in human hepatoma G2 cells by inducing apoptosis and autophagy. World J Gastroenterol. 16:4281–4290. 2010. View Article : Google Scholar : PubMed/NCBI
19	Assimakopoulos SF, Tsamandas AC, Alexandris IH, Georgiou C, Vagianos CE and Scopa CD: Stimulation of oval cell and hepatocyte proliferation by exogenous bombesin and neurotensin in partially hepatectomized rats. World J Gastrointest Pathophysiol. 2:146–154. 2011. View Article : Google Scholar : PubMed/NCBI
20	Lowes KN, Croager EJ, Olynyk JK, Abraham LJ and Yeoh GC: Oval cell-mediated liver regeneration: Role of cytokines and growth factors. J Gastroenterol Hepatol. 18:4–12. 2003. View Article : Google Scholar : PubMed/NCBI
21	Oh SH, Witek RP, Bae SH, Zheng D, Jung Y, Piscaglia AC and Petersen BE: Bone marrow-derived hepatic oval cells differentiate into hepatocytes in 2-acetylaminofluorene/partial hepatectomy-induced liver regeneration. Gastroenterology. 132:1077–1087. 2007. View Article : Google Scholar : PubMed/NCBI
22	Mavier P, Martin N, Couchie D, Préaux AM, Laperche Y and Zafrani ES: Expression of stromal cell-derived factor-1 and of its receptor CXCR4 in liver regeneration from oval cells in rat. Am J Pathol. 165:1969–1977. 2004. View Article : Google Scholar : PubMed/NCBI
23	Zhang W, Chen XP, Zhang WG, Zhang F, Xiang S, Dong HH and Zhang L: Hepatic non-parenchymal cells and extracellular matrix participate in oval cell-mediated liver regeneration. World J Gastroenterol. 15:552–560. 2009. View Article : Google Scholar : PubMed/NCBI
24	Malato Y, Ehedego H, Al-Masaoudi M, Cubero FJ, Bornemann J, Gassler N, Liedtke C, Beraza N and Trautwein C: NF-κB essential modifier is required for hepatocyte proliferation and the oval cell reaction after partial hepatectomy in mice. Gastroenterology. 143:1597–1608.e11. 2012. View Article : Google Scholar
25	Okano J, Shiota G, Matsumoto K, Yasui S, Kurimasa A, Hisatome I, Steinberg P and Murawaki Y: Hepatocyte growth factor exerts a proliferative effect on oval cells through the PI3 K/AKT signaling pathway. Biochem Biophys Res Commun. 309:298–304. 2003. View Article : Google Scholar : PubMed/NCBI
26	Chiba S: Notch signaling in stem cell systems. Stem Cells. 24:2437–2447. 2006. View Article : Google Scholar : PubMed/NCBI
27	Ge W, Martinowich K, Wu X, He F, Miyamoto A, Fan G, Weinmaster G and Sun YE: Notch signaling promotes astrogliogenesis via direct CSL-mediated glial gene activation. J Neurosci Res. 69:848–860. 2002. View Article : Google Scholar : PubMed/NCBI
28	Wang S, Sdrulla AD, diSibio G, Bush G, Nofziger D, Hicks C, Weinmaster G and Barres BA: Notch receptor activation inhibits oligodendrocyte differentiation. Neuron. 21:63–75. 1998. View Article : Google Scholar : PubMed/NCBI
29	Bouras T, Pal B, Vaillant F, Harburg G, Asselin-Labat ML, Oakes SR, Lindeman GJ and Visvader JE: Notch signaling regulates mammary stem cell function and luminal cell-fate commitment. Cell Stem Cell. 3:429–441. 2008. View Article : Google Scholar : PubMed/NCBI
30	Wang T, You N, Tao K, Wang X, Zhao G, Xia N, Li N, Tang L, Liu W and Dou K: Notch is the key factor in the process of fetal liver stem/progenitor cells differentiation into hepatocytes. Dev Growth Differ. 54:605–617. 2012. View Article : Google Scholar : PubMed/NCBI