Cluster of Differentiation 36 Deficiency Aggravates Macrophage Infiltration and Hepatic Inflammation by Upregulating Monocyte Chemotactic Protein-1 Expression of Hepatocytes Through Histone Deacetylase 2-Dependent Pathway

Zhong, Sen; Zhao, Lei; Wang, Yan; Zhang, Chang; Li, Jun; Wang, Pei; Zhou, Wei; Yang, Ping; Varghese, Zac; Moorhead, John F.; Chen, Yaxi; Ruan, Xiong Z.

doi:10.1089/ars.2016.6808

Cited by 37 publications

(31 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Noteworthy, Cd36-knockout mice were also protected against a high-carbohydrate liquid diet-induced hepatic steatosis but by a distinct mechanism regardless of hepatic fatty acid uptake and related to decreased expression of genes in the de novo lipogenesis pathway 81 . Intriguingly, Zhong et al 117 noticed that whole-body Cd36 deletion did not affect hepatic FFAs uptake in mice while increased monocyte chemotactic protein-1 transcription in hepatocytes and enhanced hepatic inflammation and fibrosis 117 , pointing out that Cd36 deficiency might contribute to NASH development by a fatty acid-independent mechanism. These somehow controversial findings indicate that further experimental research is needed to better understand the role of CD36 in regulating hepatic lipid homeostasis and its impact in the progression of hepatosteatosis to NASH.…”

Section: Role Of Cd36 In Nafldmentioning

confidence: 99%

Understanding lipotoxicity in NAFLD pathogenesis: is CD36 a key driver?

et al. 2020

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. NAFLD stages range from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH) which can progress to cirrhosis and hepatocellular carcinoma. One of the crucial events clearly involved in NAFLD progression is the lipotoxicity resulting from an excessive fatty acid (FFA) influx to hepatocytes. Hepatic lipotoxicity occurs when the capacity of the hepatocyte to manage and export FFAs as triglycerides (TGs) is overwhelmed. This review provides succinct insights into the molecular mechanisms responsible for lipotoxicity in NAFLD, including ER and oxidative stress, autophagy, lipoapotosis and inflammation. In addition, we highlight the role of CD36/FAT fatty acid translocase in NAFLD pathogenesis. Up-to-date, it is well known that CD36 increases FFA uptake and, in the liver, it drives hepatosteatosis onset and might contribute to its progression to NASH. Clinical studies have reinforced the significance of CD36 by showing increased content in the liver of NAFLD patients. Interestingly, circulating levels of a soluble form of CD36 (sCD36) are abnormally elevated in NAFLD patients and positively correlate with the histological grade of hepatic steatosis. In fact, the induction of CD36 translocation to the plasma membrane of the hepatocytes may be a determining factor in the physiopathology of hepatic steatosis in NAFLD patients. Given all these data, targeting the fatty acid translocase CD36 or some of its functional regulators may be a promising therapeutic approach for the prevention and treatment of NAFLD.

show abstract

Section: Role Of Cd36 In Nafldmentioning

confidence: 99%

Understanding lipotoxicity in NAFLD pathogenesis: is CD36 a key driver?

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In human cervical cancer cell lines, HDAC2 was reported to inhibit transcription of the expression of MHC class II genes, and antigen presentation through MHC class II is critical for activation of adaptive immune responses [ 8 ]. Cluster of differentiation 36 (CD36) could aggravate macrophage infiltration and hepatic inflammation by upregulating monocyte chemotactic protein-1 (MCP-1) expression of hepatocytes through upregulating HDAC2-dependent pathway [ 9 ]. Therefore, histone deacetylase inhibitor (HDACi) may be used to modify immunity through multiple hosts to improve the efficacy of anti-inflammation therapy.…”

Section: Introductionmentioning

confidence: 99%

The Protective Mechanism of CAY10683 on Intestinal Mucosal Barrier in Acute Liver Failure through LPS/TLR4/MyD88 Pathway

Wang

Chen

et al. 2018

Mediators of Inflammation

View full text Add to dashboard Cite

The purpose of this study was to investigate the protective mechanism of HDAC2 inhibitor CAY10683 on intestinal mucosal barrier in acute liver failure (ALF). In order to establish ALF-induced intestinal epithelial barrier disruption models, D-galactosamine/LPS and LPS were, respectively, used with rats and NCM460 cell and then administrated with CAY10683. Transepithelial electrical resistance (TEER) was measured to detect the permeability of cells. Real-time PCR and Western blotting were employed to detect the key mRNA and protein levels. The intestinal epithelial tissue pathology was detected. After interfering with CAY10683, the mRNA and protein levels of TLR4, MyD88, TRIF, and TRAF6 were decreased compared with model group (P < 0.05), whereas the levels of ZO-1 and occluding were elevated (P < 0.05). The permeability was elevated in CAY10683-interfered groups, when compared with model group (P < 0.05). And the degree of intestinal epithelial tissue pathological damage in CAY10683 group was significantly reduced. Moreover, CAY10683 significantly decreased the TLR4 staining in animal tissue. The HDAC2 inhibitor CAY10683 could promote the damage of intestinal mucosal barrier in ALF through inhibiting LPS/TLR4/MyD88 pathway.

show abstract

“…In fact, CD36 has been associated with obesity and diabetes in human diseases; Particularly, increased expression of hepatic CD36 is closely related to the development of NAFLD and non-alcoholic steatohepatitis (NASH) with insulin resistance [ 28 ]. Moreover, our previous work has demonstrated that CD36 plays an important role in balancing hepatic ROS and regulating macrophage infiltration, which could be a new potential therapeutic strategy to prevent NASH development [ 29 ]. Hence, it is believed that CD36 is emerging as a novel target for chronic liver disease.…”

Section: Discussionmentioning

confidence: 99%

Long-chain fatty acid activates hepatocytes through CD36 mediated oxidative stress

Yang

Zuo

et al. 2018

Lipids Health Dis

Self Cite

View full text Add to dashboard Cite

BackgroundAccumulating evidence suggests that activated hepatocytes are involved in the deposition of the excess extracellular matrix during liver fibrosis via the epithelial to mesenchymal transition. Lipid accumulation in hepatocytes are implicated in the pathogenesis of chronic liver injury. CD36 is known to mediate long-chain fatty acid (LCFA) uptake and lipid metabolism. However, it is unclear whether LCFA directly promotes hepatocyte activation and the involved mechanisms have not been fully clarified.MethodsMice were fed with a high fat diet (HFD) and normal hepatocyte cells (Chang liver cells) were treated with palmitic acid (PA) in vivo and in vitro. Real-time polymerase chain reaction (RT-PCR) and western blotting were used to examine the gene and protein expression of molecules involved in hepatic fibrogenesis and hepatocyte activation. CD36 was knocked down by transfecting CD36 siRNA into hepatocyte cells. Hydrogen peroxide (H2O2) and reactive oxygen species (ROS) levels were detected using commercial kits.ResultsHFD induced a profibrogenic response and up-regulated CD36 expression in vivo. Analogously, PA increased lipid accumulation and induced human hepatocyte activation in vitro, which was also accompanied by increased CD36 expression. Interestingly, knockdown of CD36 resulted in a reduction of hepatocyte lipid deposition and decreased expression of Acta2 (34% decrease), Vimentin (29% decrease), Desmin (60% decrease), and TGF-β signaling pathway related genes. In addition, HFD and PA increased the production of H2O2 in vivo (48% increase) and in vitro (385% increase), and the antioxidant, NAC, ameliorated PA-induced hepatocyte activation. Furthermore, silencing of CD36 in vitro markedly attenuated PA-induced oxidative stress (H2O2: 41% decrease; ROS: 39% decrease), and the anti-activation effects of CD36 knockdown could be abolished by pretreatment with H2O2.ConclusionsOur study demonstrated that LCFA facilitates hepatocyte activation by up-regulating oxidative stress through CD36, which could be an important mechanism in the development of hepatic fibrosis.

show abstract

Cluster of Differentiation 36 Deficiency Aggravates Macrophage Infiltration and Hepatic Inflammation by Upregulating Monocyte Chemotactic Protein-1 Expression of Hepatocytes Through Histone Deacetylase 2-Dependent Pathway

Abstract: CD36 deficiency promoted the development of NASH by facilitating the transcription of MCP-1 in hepatocytes due to the reduction of ROS and nuclear HDAC2. Antioxid. Redox Signal. 00, 000-000.

Cited by 37 publications

References 38 publications

Understanding lipotoxicity in NAFLD pathogenesis: is CD36 a key driver?

Understanding lipotoxicity in NAFLD pathogenesis: is CD36 a key driver?

The Protective Mechanism of CAY10683 on Intestinal Mucosal Barrier in Acute Liver Failure through LPS/TLR4/MyD88 Pathway

Long-chain fatty acid activates hepatocytes through CD36 mediated oxidative stress

Contact Info

Product

Resources

About