RGD Reference Report - Abnormal CD44 activation of hepatocytes with nonalcoholic fatty accumulation in rat hepatocarcinogenesis. - Rat Genome Database

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

Authors: Fang, Miao  Yao, Min  Yang, Jie  Zheng, Wen-Jie  Wang, Li  Yao, Deng-Fu 
Citation: Fang M, etal., World J Gastrointest Oncol. 2020 Jan 15;12(1):66-76. doi: 10.4251/wjgo.v12.i1.66.
RGD ID: 25823185
Pubmed: PMID:31966914   (View Abstract at PubMed)
PMCID: PMC6960074   (View Article at PubMed Central)
DOI: DOI:10.4251/wjgo.v12.i1.66   (Journal Full-text)


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 mRNA was detected by OneArray. 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 mRNA 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 mRNA (rs = 0.373, P = 0.043) and serum CD44 (rs = 0.541, P = 0.002) and between liver CD44 mRNA 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 mRNA and AFP mRNA (rs = 0.370, P = 0.044).
CONCLUSION: The data suggested that increasing CD44 expression is associated with the malignant transformation of hepatocytes in NAFLD.

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
2-acetamidofluorene  ISOCd44 (Rattus norvegicus)25823185; 258231852-Fluorenylacetamide increases CD44 mRNA in liver and and protein in liver and serumRGD 
2-acetamidofluorene  IEP 258231852-Fluorenylacetamide increases CD44 mRNA in liver and and protein in liver and serumRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to nutrient levels  IEP 25823185High-fat dietRGD 
response to organic cyclic compound  IEP 258231852-FluorenylacetamideRGD 

Objects Annotated

Genes (Rattus norvegicus)
Cd44  (CD44 molecule)

Genes (Mus musculus)
Cd44  (CD44 antigen)

Genes (Homo sapiens)
CD44  (CD44 molecule (IN blood group))


Additional Information