Fais Paolo, Leopizzi Martina, Di Maio Valeria, Longo Lucia, Della Rocca Carlo, Tagliaro Franco, Bortolotti Federica, Lo Vasco Vincenza Rita
Department of Medical and Surgical Sciences, Unit of Legal Medicine, University of Bologna, Bologna, Italy.
Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino-Sapienza University, Latina, Italy.
J Cell Biochem. 2019 May;120(5):7907-7917. doi: 10.1002/jcb.28067. Epub 2018 Nov 13.
The phosphoinositide (PI) signal transduction pathway participates in liver metabolism. Abnormal activity or expression of PI-specific phospholipase C (PLC) enzymes has been described in different liver diseases. We resume the role of the PI metabolism in liver and PLC abnormalities in different liver diseases. Moreover, we present the results of PLC analyses in a normal human liver and an alcohol-damaged liver. PLC enzymes and the expression of the corresponding genes in liver biopsies from individuals deceased for complications of the alcoholic liver disease (ALD) at different stages compared with normal controls (deceased individuals with histologically normal livers without alcohol addiction anamnesis) were analyzed by using immunohistochemistry and molecular biology techniques. The expression panel of PLCs was described in normal and alcohol abuse liver. Our observations suggest that the regulation of PLC expression might be due to posttranscriptional events and that alcohol affects the epigenetic control of PLC expression belonging to PI signaling. We also describe the alternate expression of PLCB1 and PLCH1 genes in liver. Our results corroborate literature data suggesting that PLC enzymes are differently expressed in normal versus pathological liver, playing a role in the histopathogenesis of liver tissue damage. The expression and/or localization of selected PLC isoforms is especially affected in alcohol-related liver tissue histopathology. Our present observations confirm that the modulation of protein synthesis plays a role in the regulation of PLC enzymes. We also suggest that this modulation might act at the transcription level. Further studies are required to investigate related epigenetic mechanisms.
磷酸肌醇（PI）信号转导途径参与肝脏代谢。在不同的肝脏疾病中，PI特异性磷脂酶C（PLC）酶的活性或表达异常已有相关描述。我们总结了PI代谢在肝脏中的作用以及不同肝脏疾病中PLC的异常情况。此外，我们展示了在正常人类肝脏和酒精损伤肝脏中PLC分析的结果。通过免疫组织化学和分子生物学技术，分析了因酒精性肝病（ALD）并发症死亡的个体在不同阶段的肝脏活检组织中PLC酶及其相应基因的表达情况，并与正常对照（组织学正常且无酒精成瘾病史的死亡个体）进行比较。描述了正常肝脏和酒精滥用肝脏中PLC的表达谱。我们的观察结果表明，PLC表达的调节可能归因于转录后事件，并且酒精会影响属于PI信号传导的PLC表达的表观遗传控制。我们还描述了肝脏中PLCB1和PLCH1基因的交替表达。我们的结果证实了文献数据，表明PLC酶在正常肝脏与病理肝脏中的表达不同，在肝组织损伤的组织病理学发生中起作用。在酒精相关的肝组织病理学中，所选PLC同工型的表达和/或定位受到特别影响。我们目前的观察结果证实，蛋白质合成的调节在PLC酶的调节中起作用。我们还认为这种调节可能在转录水平起作用。需要进一步研究来调查相关的表观遗传机制。
