Abnormal CD44 activation of hepatocytes with nonalcoholic fatty accumulation in rat hepatocarcinogenesis

更新时间:2023-05-28

【摘要】BACKGROUND Prevalence of nonalcoholic fatty liver disease(NAFLD) is rapidly increasing,and NAFLD has become one of the most common chronic liver diseases worldwide.With abnormal CD44 activation,the severe form of NAFLD can progress to liver cirrhosis and hepatocellular carcinoma(HCC).Thus,the molecular mechanism of CD44 in NAFLD needs to be identified.AIM To investigate the relationship between CD44 activation and malignant transformation of rat hepatocytes under nonalcoholic lipid accumulation.METHODS Sprague-Dawley rats were fed a high-fat(HF) for 12 wk to entice NAFLD and then with HF plus 2-fluorenylacetamide(0.05%) to induce HCC.Rats were sacrificed every 2 wk,and subsequently divided into the groups based on liver pathological examination(hematoxylin and eosin staining):NAFLD,denaturation,precancerosis,HCC,and control.Liver CD44 m RNA was detected by One Array.Liver fat as assessed by Oil red O staining or CD44 by immunohistochemical assay was compared with their integral optic density.Serum CD44,alanine aminotransferase,aspartate aminotransferase,triglyceride,total cholesterol,and AFP levels were quantitatively tested.RESULTS Elevated CD44 was first reported in hepatocarcinogenesis,with increasing expression from NAFLD to HCC at the protein or m RNA level.The CD44 integral optic density values were significantly different between the control group and the NAFLD(t = 25.433,P < 0.001),denaturation(t = 48.822,P < 0.001),precancerosis(t = 27.751,P < 0.001),and HCC(t = 16.239,P < 0.001) groups,respectively.Hepatic CD44 can be secreted into the blood,and serum CD44 levels in HCC or precancerous rats were significantly higher(P < 0.001) than those in any of the other rats.Positive correlations were found between liver CD44 and CD44 m RNA(rs = 0.373,P = 0.043) and serum CD44(rs = 0.541,P = 0.002) and between liver CD44 m RNA and serum CD44(rs = 0.507,P = 0.004).Moreover,significant correlations were found between liver CD44 and liver AFP(rs = 0.572,P = 0.001),between serum CD44 and serum AFP(rs = 0.608,P < 0.001),and between CD44 m RNA and AFP m RNA(rs = 0.370,P = 0.044).CONCLUSION The data suggested that increasing CD44 expression is associated with the malignant transformation of hepatocytes in NAFLD.

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