Laish Ido, Mannasse-Green Batya, Hadary Ruth, Biron-Shental Tal, Konikoff Fred M, Amiel Aliza, Kitay-Cohen Yona
Gastroenterology and Hepatology Institute, Meir Medical Center, Kfar Saba, Israel.
Cytogenet Genome Res. 2016;150(2):93-99. doi: 10.1159/000454654. Epub 2016 Dec 23.
Nonalcoholic fatty liver disease (NAFLD) and cryptogenic cirrhosis (CC) are considered preneoplastic conditions that might progress to hepatocellular carcinoma. We evaluated parameters of telomere dysfunction in these patient groups to study the correlation between telomere length and the progression of NAFLD. We analyzed peripheral lymphocytes from 22 patients with NAFLD, 20 patients with CC, and 20 healthy, age-matched controls. Telomere length was analyzed using quantitative fluorescence in situ hybridization, and cellular senescence was evaluated by the percentage of cells with senescence-associated heterochromatin foci. The expression of telomerase reverse transcriptase (hTERT) mRNA was measured using polymerase chain reaction, and telomere capture (TC) was assessed with 2 Cytocell probes, 15qter and 13qter. Shorter telomere length and increased cellular senescence was demonstrated in patients with NAFLD, compared to the CC patients and healthy controls. While hTERT mRNA was significantly decreased, TC was increased in CC patients, compared to the NAFLD group and healthy individuals. Thus, there is a correlation between hTERT mRNA expression and telomere length in patients with NAFLD, which might be related to associated metabolic disorders and the risk of malignant transformation. Patients with CC, on the contrary, elongate their telomeres through the TC mechanism.
非酒精性脂肪性肝病(NAFLD)和隐源性肝硬化(CC)被认为是可能进展为肝细胞癌的癌前病变。我们评估了这些患者组中端粒功能障碍的参数,以研究端粒长度与NAFLD进展之间的相关性。我们分析了22例NAFLD患者、20例CC患者和20名年龄匹配的健康对照者的外周血淋巴细胞。使用定量荧光原位杂交分析端粒长度,通过具有衰老相关异染色质灶的细胞百分比评估细胞衰老。使用聚合酶链反应测量端粒酶逆转录酶(hTERT)mRNA的表达,并使用2种Cytocell探针(15qter和13qter)评估端粒捕获(TC)。与CC患者和健康对照相比,NAFLD患者表现出较短的端粒长度和增加的细胞衰老。与NAFLD组和健康个体相比,CC患者的hTERT mRNA显著降低,而TC增加。因此,NAFLD患者的hTERT mRNA表达与端粒长度之间存在相关性,这可能与相关的代谢紊乱和恶性转化风险有关。相反,CC患者通过TC机制延长其端粒。