Keratinocyte growth factor protects endometrial cells from oxygen glucose deprivation/re-oxygenation via activating Nrf2 signaling

Shi, Xiaokai; Liu, Haiyan; Li, Shuping; Xu, Hongbin

doi:10.1016/j.bbrc.2018.04.208

Cited by 30 publications

(68 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lenti-CRISPR-green fluorescent protein (GFP)-Nrf2 knockout (KO) construct was provided by Dr. Li [30]. The construct was transfected to THP-1 cells using Lipofectamine 2000 (Invitrogen, Carlsbad, CA).…”

Section: Nrf2 Knockoutmentioning

confidence: 99%

4-Octyl Itaconate Activates Nrf2 Signaling to Inhibit Pro-Inflammatory Cytokine Production in Peripheral Blood Mononuclear Cells of Systemic Lupus Erythematosus Patients

Tang¹,

Wang²,

Xie³

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Increased production of multiple pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, plays an essential pathogenic role in the progression of systemic lupus erythematosus (SLE). Recent studies have characterized itaconate as a novel and potent nuclear-factor-E2-related factor 2 (Nrf2) activator that activates Nrf2 signaling by alkylating cysteine residues on Keap1 (Kelch-like ECH-associated protein 1). Methods: THP-1 human macrophages and peripheral blood mononuclear cells (PBMCs) of SLE patients were treated with 4-octyl itaconate (OI). Nrf2 signaling activation was tested by qPCR assay and western blotting. mRNA expression and the production of multiple pro-inflammatory cytokines were tested by qPCR and enzyme-linked immunosorbent assays, respectively. Nuclear factor (NF)-κB activation was tested by the p65 DNA-binding assay. Results: We demonstrated that OI, the cell-permeable derivative of itaconate, induced Keap1-Nrf2 dissociation, Nrf2 protein accumulation, and nuclear translocation, which enabled the transcription and expression of multiple Nrf2-dependentantioxidant enzymes (heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1, and glutamate-cysteine ligase modifier subunit) in THP-1 human macrophages. OI also induced significant Nrf2 activation in SLE patient-derived PBMCs. OI pretreatment inhibited mRNA expression and the production of multiple pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in SLE patient-derived PBMCs and lipopolysaccharide (LPS)-activated THP-1 cells. OI potently inhibited NF-κB activation in SLE patient-derived PBMCs and LPS-activated THP-1 cells. Importantly, Nrf2 silencing (by targeted short hairpin RNA) or knockout (by CRISPR/Cas9 gene-editing method) almost abolished OI-induced anti-oxidant and anti-inflammatory actions in SLE patient-derived PBMCs and LPS-activated THP-1 cells. Conclusion: OI activates Nrf2 signaling to inhibit the production of pro-inflammatory cytokines in human macrophages and SLE patient-derived PBMCs. OI and itaconate could have important therapeutic value for the treatment of SLE.

show abstract

Section: Nrf2 Knockoutmentioning

confidence: 99%

4-Octyl Itaconate Activates Nrf2 Signaling to Inhibit Pro-Inflammatory Cytokine Production in Peripheral Blood Mononuclear Cells of Systemic Lupus Erythematosus Patients

Tang¹,

Wang²,

Xie³

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Post-transcriptional modifications of Nrf2 are essential for its activation [14]. Nrf2 Ser-40 phosphorylation can induce Nrf2-Keap1 departure [38], enabling Nrf2 protein stabilization, accumulation, and nuclear translocation [21,23,26,29]. Our results showed that CNTF activated Akt signaling, serving as a upstream signaling for Nrf2 Ser-40 phosphorylation and activation.…”

Section: Discussionmentioning

confidence: 60%

“…Akt could be a upstream signaling of Nrf2 via phosphorylating Nrf2 at Ser-40 [21,23,26,29]. Here, we found that CNTF dose-dependently induced Akt activation in H9c2 cells (Fig.…”

Section: Akt Activation Mediates Cntf-induced Nrf2 Activation and Myomentioning

confidence: 53%

“…OGDR mainly induces programmed necrosis, but not apoptosis, in myocardial cells and other cells [5,23,27,28]. Indeed, OGDR treatment in H9c2 cells induced programmed necrosis, which was evidenced by mitochondrial ANT-1-p53-Cyp-D association (Fig.…”

Section: Cntf Protects Myocardial Cells From Ogd/re-oxygenationmentioning

confidence: 86%

“…Additionally, the Nrf2-knockout-C R I S P R / C a s 9 lentiviral construct (a gift from Dr [23].) was transfected to H9c2 cells to establish Nrf2-knockout cells.…”

Section: Nrf2 Silencing or Knockout Abolishes C N T F -I N D U C E D mentioning

confidence: 99%

See 2 more Smart Citations

Ciliary Neurotrophic Factor (CNTF) Protects Myocardial Cells from Oxygen Glucose Deprivation (OGD)/Re-Oxygenation via Activation of Akt-Nrf2 Signaling

Zheng¹,

Zhang²,

Sheng³

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Oxygen glucose deprivation (OGD)/re-oxygenation (OGDR) exposure to myocardial cells mimics ischemia-reperfusion injuries. We studied the potential activity of ciliary neurotrophic factor (CNTF) on OGDR-treated myocardial cells. Methods: CNTF and CNTFR expression were tested by RT-PCR assay and Western blotting assay. Cell viability and death were tested by MTT assay and LDH release assay, respectively. Akt-Nrf2 signalings were tested by Western blotting assay and qPCR assay. Results: CNTF and its receptor CNTFR were functionally expressed in established H9c2 myocardial cells and primary murine myocardiocytes. Pretreatment of CNTF significantly attenuated OGDR-induced viability reduction and death in myocardial cells. Further studies show that in the myocardial cells CNTF activated NF-E2-related factor 2 (Nrf2) signaling to inhibit OGDR-induced reactive oxygen species (ROS) production and programmed necrosis, preventing adenine nucleotide translocator 1 (ANT-1)-p53-cyclophilin D (Cyp-D) mitochondrial association and mitochondrial depolarization. Nrf2 silencing or knockout almost abolished CNTF-induced H9c2 cytoprotection against OGDR. CNTF activated Akt in H9c2 cells and primary murine myocardiocytes. Conversely, Akt blockage by the pharmacological inhibitors not only blocked CNTF-induced Nrf2 Ser-40 phosphorylation and activation, but also nullified anti-OGDR actions by CNTF in myocardial cells. Conclusion: CNTF activates Akt-Nrf2 signaling to protect myocardial cells from OGDR.

show abstract

Mesenchymal stem cells overexpressing heme oxygenase‐1 ameliorate lipopolysaccharide‐induced acute lung injury in rats

Chen

Tang

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common and potentially lethal clinical syndromes characterized by acute respiratory failure resulting from excessive pulmonary inflammation, noncardiogenic pulmonary edema, and alveolar-capillary barrier disruption. At present, there is no effective and specific therapy for ALI/ARDS. Mesenchymal stem cells (MSCs) have well-known therapeutic potential in patients with ALI/ARDS. Heme oxygenase-1 (HO-1), a cytoprotective enzyme, possesses antioxidative, anti-inflammatory, and antiapoptotic effects. Thus, a combination of MSC transplantation with HO-1 delivery may have an additional protective effect against ALI/ARDS. This study investigated the effect of HO-1modified bone-marrow-derived MSCs (MSCs-HO-1) on lipopolysaccharide (LPS)induced ALI and its underlying mechanisms. We established MSCs-HO-1 through lentiviral transduction. The ALI rat model was established by successive LPS inhalations following injection with MSCs-HO-1. The survival rate, histological changes in the lungs, total protein concentration and neutrophil counts in bronchoalveolar lavage fluid, lung wet/dry weight ratio, cytokine levels in serum and lungs, nuclear transcription factor-κB activity, and protein expression of Toll-like receptor 4 signaling adaptors were examined. Furthermore, the cell viability, apoptosis, and paracrine activity of MSCs-HO-1 were examined under inflammatory stimuli in vitro. MSCs-HO-1 injection improved these parameters compared with primary unmodified MSCs. Moreover, MSCs-HO-1 had superior prosurvival and antiapoptotic properties and enhanced paracrine functions in vitro. Therefore, MSCs-HO-1 exert an enhanced protective effect to alleviate LPS-induced ALI in rats, and the mechanisms may be partially associated with superior prosurvival, antiapoptosis, and enhanced paracrine functions of MSCs-HO-1. These findings provide a novel insight into MSC-based therapeutic strategies for treating ALI/ARDS. K E Y W O R D S acute lung injury, heme oxygenase-1, lipopolysaccharide, mesenchymal stem cells, RRID

show abstract

Keratinocyte growth factor protects endometrial cells from oxygen glucose deprivation/re-oxygenation via activating Nrf2 signaling

Cited by 30 publications

References 35 publications

4-Octyl Itaconate Activates Nrf2 Signaling to Inhibit Pro-Inflammatory Cytokine Production in Peripheral Blood Mononuclear Cells of Systemic Lupus Erythematosus Patients

4-Octyl Itaconate Activates Nrf2 Signaling to Inhibit Pro-Inflammatory Cytokine Production in Peripheral Blood Mononuclear Cells of Systemic Lupus Erythematosus Patients

Ciliary Neurotrophic Factor (CNTF) Protects Myocardial Cells from Oxygen Glucose Deprivation (OGD)/Re-Oxygenation via Activation of Akt-Nrf2 Signaling

Mesenchymal stem cells overexpressing heme oxygenase‐1 ameliorate lipopolysaccharide‐induced acute lung injury in rats

Contact Info

Product

Resources

About