RESEARCH PAPER
PDGF-BB homodimer serum level – a good indicator of the severity of alcoholic liver cirrhosis
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1
Medical University, Lublin, Poland
2
University of Life Sciences, Lublin, Poland
3
Institute of Rural Health, Lublin, Poland
Corresponding author
Ewa Kurys-Denis
Medical University of Lublin, ul.St.Staszica 16, 20-081, Lublin, Poland
Ann Agric Environ Med. 2020;27(1):80-85
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Liver cirrhosis is a chronic disease in which progressive fibrosis is noted. This process leads to changed architectonics of the liver parenchyma and the appearance of regenerative nodules, all of which are caused by pathological activation of the hepatic stellate cells. This process is enhanced on a molecular level by many cytokines, with platelet-derived growth factors (PDGFs) playing the key role.
Objective:
The aim of the study was to assess serum concentrations of PDGFs active biodymers (PDGF-AA, PDGF-BB and PDGF-AB) in patients with alcoholic liver cirrhosis, and to correlate them with the stage of disease.
Material and methods:
64 patients with alcoholic cirrhosis and a control group of 16 healthy individuals were analysed. Liver cirrhosis was determined based on clinical image, history of the patients’ alcohol consumption, laboratory findings and abdominal ultrasonography. The serum PDGF-AA, PDGF-BB and PDGF-AB concentrations were determined using ELISA kits.
Results:
Serum concentration of PDGF-AA and PDGF-BB homodimers increases in patients with alcoholic liver cirrhosis (p=0.034 and p<0.0001, respectively), unlike the serum concentration of PDGF-AB heterodimer (p>0.05). When the stage of the disease increases, the concentrations of PDGF-AA and PGFD-BB in blood also oncrease. Furthermore, the serum level of both PDGF-AA and PDGF-BB correlates significantly with the severity of alcoholic liver cirrhosis (measured by Pugh-Child’s scale), the correlation being stronger in the case of PDGF-BB levels than PDGF-AA (R=0.28; p=0.027 and R=0.26; p=0.038, respectively).
Conclusions:
The plasma levels of PDGF-AA and -BB may be indicators of alcohol-induced liver fibrosis process, and might be considered as future possible treatment targets, with PDGF-BB levels being an even better indicator than PDGF-AA levels.
REFERENCES (24)
1.
Blachier M, Leleu H, Peck-Radosavljevic M, Valla D-C, Roudot Thoraval F. The burden of liver disease in Europe: A review of available epidemiological data. J Hepatol. 2013; 25(3): 593–608.
2.
World Health Organization. European status report on alcohol and health: World Health Organization. Regional Office for Europe, 2010.
3.
Plewka K, Szuster-Ciesielska A, Kandefer-Szerszeń M. Role of stellate cells in alcoholic liver fibrosis. Postepy Hig Med Dosw. 2009; 63: 303–317.
4.
Reeves HL, Friedman SL. Activation of setellate cells – a key issue in liver fibrosis. Front Biosci. 2002; 7: d808–d826.
5.
Zhou W-C, Zhang Q-B, Qiao L. Pathogenesis of liver cirrhosis. World J Gastroenterol. 2014; 20(23): 7312–7324.
6.
Zhang BB, Cai WM, Weng HL, Hu ZR, Lu J, Zheng M, et al. Diagnostic value of platelet derived growth factor-BB, transforming growth factor-b1, matrix metalloproteinase-1, and tissue inhibitor of matrix metalloproteinase-1 in serum and peripheral blood mononuclear cells for hepatic fibrosis. World J Gastroenterol. 2003; 9(11): 2490–2496.
7.
Hua-Zhong Y, Qin Ch, Wen-You Z et al. PDGF signaling pathway in hepatic fibrosis pathogenesis and therapeutics (Review). Molecular Med Rep. 2017; 16: 7879–7889.
8.
Fredriksson L, Li H and Eriksson U: The PDGF family: Four gene products from five dimeric isoforms. Cytokine Growth Factor Rev. 2004; 15: 197-204.
9.
Betsholtz C. Biology of platelet-derived growth factors in development. Birth Defects Res C Embryo Today. 2003; 69(4): 272–85.
10.
Breitkopf K, van Roeyen CV, Sawitza I, Wickert L, Floege J, Gressner AM. Expression patterns of PDGF-A, -B, -C and -D and the PDGF-receptors alpha and beta in activated rat hepatic stellate cells (HSC). Cytokine. 2005; 31(5): 349–57.
11.
Diang XC1, Ma LN, Li YF, Liu XY, Zhang X, Liu JY et al. Association between serum platelet-derived growth factor BB and degree of liver damage, fibrosis and hepatitis B e antigen (HBeAg) status in CHB patients. Hepatogastroenterology. 2012; 59(120): 2357–60.
12.
Tanikawa AA, Tommasini Grotto RM, Faria Silva G, Camargo Ferrasi A, Rodrigues Sarnighausen VC, de Moura Campos Pardini MI. Platelet-derived growth factor A mRNA in platelets is associated with the degree of hepatic fibrosis in chronic hepatitis C. Rev Soc Bras Med Trop. 2017; 50(1): 113–116.
13.
Folestad E, Kunath A, Wagsater D. PDGF-C and PDGF-D signaling in vascular diseases and animal models. Molecular Aspect Med. 2018; 62: 1–11.
14.
Klinkhammer BM, Floege J, Boor P. PDGF in organ fibrosis. Molecular Aspect Med. 2017; 1–19.
15.
Pugh R, Murray-Lyon I, Dawson J, Pietroni M, et al. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973; 60(8): 646–9.
16.
Papadopoulos N, Lennartsson J. The PDGF/PDGFR pathway as a drug target. Molecular Aspects Med. 2017: 1–14.
17.
Thieringer F, Maass T, Czochra P, Klopcic B, Conrad I, Friebe D, et al. Spontaneous hepatic fibrosis in transgenic mice overexpressing PDGF-A. Gene. 2008; 423(1): 23–28.
18.
Friedman SL. Liver fibrosis e from bench to bedside. J. Hepatol. 2003; 1(38): S38-S53.
19.
Zoubek ME, Trautwein C, Strnad P. Reversal of liver fibrosis: from fiction treality. Best Pract Res Clin Gastroenterol. 2017; 31(2): 129–141.
20.
Marcellin P, Gane E, Buti et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet 2013; 381 (9865): 468–475.
21.
Poynard T, McHutchison J, Manns et al. Impact of pegylated interferon alfa-2b and riba-virin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology 2002; 122(5): 1303–1313.
22.
Van Dijk F, Olinga P, Poelstra K and Beljaars L. Targeted therapies in liver fibrosis: combining the best parts of platelet-derived growth factor BB and interferon gamma. Frontiers in Medicine 2015; 2: 72.
23.
Ruchi Shah, Karina Reyes-Gordillo and Marcos Rojkind. Thymosin β4 inhibits PDGF-BB induced activation, proliferation, and migration of human hepatic stellate cells via its actin-binding domain. Exp Opinion Biol Ther. 2018;18:sup1: 177–184.
24.
Borkham-Kamphorst E, Weiskirchen R. The PDGF system and its antagonists in liver fibrosis, Cytokine Growth Factor Rev. 2016; 28: 53–61.