PICK1 confers anti-inflammatory effects in acute liver injury via suppressing M1 macrophage polarization

Xie, Juan; Wu, Xiaoqin; Zhou, Qun; Yang, Yang; Tian, Ye; Huang, Cheng; Meng, Xiao‐Ming; Li, Jun

doi:10.1016/j.biochi.2016.05.002

Cited by 21 publications

(16 citation statements)

References 60 publications

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“…In the study presented here, we found that ginsenoside Rg3 significantly inhibited the increases of the pro-inflammatory cytokines TNF-α, IL-1β and IL-6 as well as prevented the decreases of anti-inflammatory cytokines IL-10 and TGF-β after LPS stimulation. The process by which macrophage activation induced different subtypes to respond to changes in the environment is generally called polarization, and the phenotype of polarization can be divided into M1 and M2 ( Xie et al, 2016 ). The polarization of M2 macrophages appears to promote the release of anti-inflammatory and immunosuppressive agents as well as motivate the repair and healing of damaged tissue ( Arnold et al, 2007 ; Kang et al, 2008 ).…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg3 Attenuates Lipopolysaccharide-Induced Acute Lung Injury via MerTK-Dependent Activation of the PI3K/AKT/mTOR Pathway

Yang

Wang

et al. 2018

Front. Pharmacol.

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Acute lung injury (ALI) is a common clinical disease with high morbidity in both humans and animals. Ginsenoside Rg3, a type of traditional Chinese medicine extracted from ginseng, is widely used to cure many inflammation-related diseases. However, the specific molecular mechanism of the effects of ginsenoside Rg3 on inflammation has rarely been reported. Thus, we established a mouse model of lipopolysaccharide (LPS)-induced ALI to investigate the immune protective effects of ginsenoside Rg3 and explore its molecular mechanism. In wild type (WT) mice, we found that ginsenoside Rg3 treatment significantly mitigated pathological damages and reduced myeloperoxidase (MPO) activity as well as the production of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6); furthermore, the production of anti-inflammatory mediators interleukin-10 (IL-10) and transforming growth factor-β (TGF-β), polarization of M2 macrophages and expression levels of the phosphorylation of phosphatidylinositol 3-hydroxy kinase (PI3K), protein kinase B (PKB, also known as AKT), mammalian target of rapamycin (mTOR) and Mer receptor tyrosine kinase (MerTK) were promoted. However, there were no significant differences with regards to the pathological damage, MPO levels, inflammatory cytokine levels, and protein expression levels of the phosphorylation of PI3K, AKT and mTOR between the LPS treatment group and ginsenoside Rg3 group in MerTK-/- mice. Taken together, the present study demonstrated that ginsenoside Rg3 could attenuate LPS-induced ALI by decreasing the levels of pro-inflammatory mediators and increasing the production of anti-inflammatory cytokines. These processes were mediated through MerTK-dependent activation of its downstream the PI3K/AKT/mTOR pathway. These findings identified a new site of the specific anti-inflammatory mechanism of ginsenoside Rg3.

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Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg3 Attenuates Lipopolysaccharide-Induced Acute Lung Injury via MerTK-Dependent Activation of the PI3K/AKT/mTOR Pathway

Yang

Wang

et al. 2018

Front. Pharmacol.

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“…Besides, PICK1 influences the progress of acrosome biogenesis, and its deficiency is accompanied by increased apoptosis [ 15 ]. PICK1 is also proved to have an anti-inflammatory role in LPS-induced acute liver injury by suppressing macrophage polarization [ 16 ]. A recent study showed that the failure of PICK1 localization to nucleus-associated acrosomic vesicles influences acrosome biogenesis in Sirtuin-1-deficient germ cells, and the progress was associated with disrupted autophagic flux [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

PICK1 Deficiency Induces Autophagy Dysfunction via Lysosomal Impairment and Amplifies Sepsis-Induced Acute Lung Injury

Lou

Zhang

et al. 2018

Mediators of Inflammation

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Sepsis is a systemic inflammatory reaction caused by infection. Multiple organ failure ultimately leads to high morbidity and mortality. Unfortunately, therapies against these responses have been unsuccessful due to the insufficient underlying pathophysiological evidence. Protein interacting with C-kinase 1 (PICK1) has received considerable attention because of its important physiological functions in many tissues. However, its role in sepsis-induced acute lung injury (ALI) is unclear. In this study, we used cecal ligation and puncture (CLP) to establish a septic model and found that decreased microtubule-associated protein-1light chain 3 (LC3)-II/LC3-I in PICK1−/− septic mice was caused by autophagy dysfunction. Consistently, the transmission electron microscopy (TEM) of bone marrow-derived macrophages (BMDMs) from PICK1−/− mice showed the accumulation of autophagosomes as well. However, more serious damage was caused by PICK1 deficiency indicating that the disrupted autophagic flux was harmful to sepsis-induced ALI. We also observed that it was the impaired lysosomal function that mediated autophagic flux blockade, and the autophagy progress was relevant to PI3K-Akt-mTOR pathway. These findings will aid in the potential development of PICK1 with novel evidence of autophagy in sepsis treatment and prevention.

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“…This particular structure enables PICK1 to bind to various membrane proteins, thus initiating multiple functions [ 20 – 22 ]. PICK1 is widely expressed in various organs and has been found to participate in the oxidative regulation by regulating glutathione (GSH, an important antioxidant) [ 23 ] in the lung [ 24 ] and liver [ 25 ]. However, the research on the relationship between PICK1 and SA-AKI is relatively rare.…”

Section: Introductionmentioning

confidence: 99%

PICK1 Deficiency Exacerbates Sepsis-Associated Acute Kidney Injury

Dou

Tong

Yang

et al. 2021

BioMed Research International

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We performed in vitro and in vivo experiments to explore the role of protein kinase C-binding protein 1 (PICK1), an intracellular transporter involved in oxidative stress-related neuronal diseases, in sepsis-related acute kidney injury (AKI). Firstly, PCR, western blotting, and immunohistochemistry were used to observe the expression of PICK1 after lipopolysaccharide- (LPS-) induced AKI. Secondly, by inhibiting PICK1 in vivo and silencing PICK1 in vitro, we further explored the effect of PICK1 on AKI. Finally, the relationship between PICK1 and oxidative stress and the related mechanisms were explored. We found that the expression of PICK1 was increased in LPS-induced AKI models both in vitro and in vivo. PICK1 silencing significantly aggravated LPS-induced apoptosis, accompanied by ROS production in renal tubular epithelial cells. FSC231, a PICK1-specific inhibitor, aggravated LPS-induced kidney injury. Besides, NAC (N-acetylcysteine), a potent ROS scavenger, significantly inhibited the PICK1-silencing-induced apoptosis. In conclusion, PICK1 might protect renal tubular epithelial cells from LPS-induced apoptosis by reducing excessive ROS, making PICK1 a promising preventive target in LPS-induced AKI.

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PICK1 confers anti-inflammatory effects in acute liver injury via suppressing M1 macrophage polarization

Cited by 21 publications

References 60 publications

Ginsenoside Rg3 Attenuates Lipopolysaccharide-Induced Acute Lung Injury via MerTK-Dependent Activation of the PI3K/AKT/mTOR Pathway

Ginsenoside Rg3 Attenuates Lipopolysaccharide-Induced Acute Lung Injury via MerTK-Dependent Activation of the PI3K/AKT/mTOR Pathway

PICK1 Deficiency Induces Autophagy Dysfunction via Lysosomal Impairment and Amplifies Sepsis-Induced Acute Lung Injury

PICK1 Deficiency Exacerbates Sepsis-Associated Acute Kidney Injury

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