Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

19 March 2020 : Laboratory Research  

The p66shc-Mediated Regulation of Hepatocyte Senescence Influences Hepatic Steatosis in Nonalcoholic Fatty Liver Disease

Jing Zhang1BDE, Yanpeng Li2EF, Bingyuan Wang3AD, Yan Luo4CG, Junping Shi5AG*, Baiyun Zhao6FG

DOI: 10.12659/MSM.921887

Med Sci Monit 2020; 26:e921887


BACKGROUND: Recent studies have suggested that hepatocyte senescence could contribute to hepatic steatosis and its progression in nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanism causing hepatocyte senescence in this pathological condition is still unclear. A thorough understanding of the mechanism could provide a new target for therapeutic intervention. The purpose of this study was to investigate the role of p66shc in hepatocyte senescence and hepatocyte damage in NAFLD progression.

MATERIAL AND METHODS: We examined the expression levels of hepatic p66shc and senescence markers in rats and humans with NAFLD, and we assessed the effect of p66shc knockdown or overexpression on senescence and steatosis in human liver cells.

RESULTS: In this study, we showed that increased hepatic p66shc expression was consistent with upregulated expression of the following senescence markers in NAFLD rats: heterochromatin protein-1-beta (HP1β), p16, p21, and p53. Furthermore, senescence and steatosis could be induced in hepatoblastoma cell line (HepG2) cells when cells were stimulated with a low concentration of H₂O₂, and this effect was significantly alleviated by knockdown of p66shc. However, overexpression of p66shc could promote senescence and steatosis in L02 cells. Finally, increased hepatic p66shc protein levels correlated with enhanced expression of the senescence marker p21 and mirrored the degree of disease severity in NAFLD patients.

CONCLUSIONS: Our findings indicated that the increase in hepatocyte senescence and steatosis in NAFLD may be caused by the upregulation of p66shc expression, implying that strategies for p66shc-mediated regulation of hepatocyte senescence may provide new therapeutic tools for NAFLD.

Keywords: Cell Aging, Fatty Liver, Shc Signaling Adaptor Proteins, Disease Progression, Hep G2 Cells, Hepatocytes, Non-alcoholic fatty liver disease, Src Homology 2 Domain-Containing, Transforming Protein 1


Med Sci Monit 2020; 26:e926160     https://medscimonit.com/abstract/index/idArt/926160

The authors informed the journal that a few errors occurred in their manuscript.
1. The picture of L02/p66shc in Figure 5C of the published manuscript is incorrect and has been replaced the corrected one in Figure 5 shown below.
2. The ordinate of p21 mRNA expression histogram which is “0, 5, 10, 15, 20” is also incorrect, and it has been corrected to “0.0, 0.5, 1.0, 1.5, 2.0” in the Figure 5 shown below.
3. The ordinate of p66shc/GAPDH protein and p21/GAPDH protein histogram which is “0.0, 0.2, 0.4, 06., 0.8, 1.0” is also incorrect, and it has been corrected to “0.0, 0.2, 0.4, 0.6, 0.8, 1.0” in the Figure 5 shown below.


01 March 2023 : Editorial  

Editorial: Global Surveillance of Highly Pathogenic Avian Influenza Viruses in Poultry, Wild Birds, and Mammals to Prevent a Human Influenza Pandemic

Dinah V. Parums

DOI: 10.12659/MSM.939968

Med Sci Monit 2023; 29:e939968


03 March 2023 : Database Analysis  

Reinfections from SARS-CoV-2: A Retrospective Study from the Gyncentrum Genetic Laboratory in Sosnowiec, Po...

Med Sci Monit In Press; DOI: 10.12659/MSM.939452  

09 February 2023 : Clinical Research  

Evaluation of Health-Related Quality of Life and Mental Health in 729 Medical Students in Indonesia During ...

Med Sci Monit 2023; 29:e938892

27 December 2022 : Clinical Research  

Effect of Physiotherapy to Correct Rounded Shoulder Posture in 30 Patients During the COVID-19 Pandemic in ...

Med Sci Monit 2022; 28:e938926

In Press

21 Mar 2023 : Clinical Research  

Efficacy of Direct Anterior Approach Versus Posterior Lateral Approach for Total Hip Replacement in Patient...

Med Sci Monit In Press; DOI: 10.12659/MSM.939682  

21 Mar 2023 : Clinical Research  

Intraoperative Hypotension and Its Association with Postoperative Acute Kidney Injury in Patients Undergoin...

Med Sci Monit In Press; DOI: 10.12659/MSM.938945  

20 Mar 2023 : Clinical Research  

Management of Unstable C1 Fractures Involving the Lateral Mass: Posterior C1-C2 Screw-Rod Fixation and Fusion

Med Sci Monit In Press; DOI: 10.12659/MSM.938600  

17 Mar 2023 : Clinical Research  

Relationship Between Autonomic Nervous System Activity and Axial Length in Children

Med Sci Monit In Press; DOI: 10.12659/MSM.939451  

Most Viewed Current Articles

13 Nov 2021 : Clinical Research  

Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...

DOI :10.12659/MSM.932788

Med Sci Monit 2021; 27:e932788

30 Dec 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

DOI :10.12659/MSM.935379

Med Sci Monit 2021; 27:e935379

08 Mar 2022 : Review article  

A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...

DOI :10.12659/MSM.936292

Med Sci Monit 2022; 28:e936292

01 Jan 2022 : Editorial  

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750