Protective effects of recombinant human cytoglobin against chronic alcohol-induced liver disease in vivo and in vitro

Wen, Jian; Wu, Yongbin; Wei, Wei; Li, Zhen; Wang, Ping; Zhu, Shiwei; Wang, Dong

doi:10.1038/srep41647

Cited by 14 publications

(21 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, in a study of an alcoholic liver disease model, treatment with recombinant human Cygb significantly inhibited Kupffer cell (KC) proliferation and tumor necrosis factor-alpha (TNF-α) expression, in LPS-stimulated KCs. Cygb also inhibited LPS-induced NADPH oxidase activity and ROS, NO, and O 2 •− generation (Wen et al, 2017). In addition, Cygb-deficient mice exhibited increased inflammation (Thuy et al, 2015;Van Thuy et al, 2017), as well as increased expression of TNF-α mRNA and many genes associated with inflammation (Yassin et al, 2018).…”

Section: Introductionmentioning

confidence: 91%

“…Primary rat cultures were prepared as previously described (Soares et al, 2013). To stimulate the cells, they were incubated with LPS (Sigma-Aldrich, St. Louis, MO, USA; 10 µg/ml) or recombinant rat Cygb (Cusabio Technology, Houston, TX, USA; 10 and 20 µg/ml) for 4 h. The concentrations of LPS and Cygb used were based on previous studies (Wen et al, 2017;Leisengang et al, 2018). PBS was used as a negative control.…”

Section: Preoptic Area Primary Cell Culturesmentioning

confidence: 99%

See 1 more Smart Citation

Cytoglobin Attenuates Neuroinflammation in Lipopolysaccharide-Activated Primary Preoptic Area Cells via NF-κB Pathway Inhibition

Gomes

Sousa

Ott

et al. 2019

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Cytoglobin (Cygb) is a hexacoordinate protein, associated with the transport of oxygen, nitric oxide scavenging, tumor suppression and protection against oxidative stress and inflammation. This protein is expressed in brain areas including the preoptic area (POA) of the anterior hypothalamus, the region responsible for the regulation of body temperature. In this study, we show that Cygb is upregulated in the rat hypothalamus 2.5 h and 5 h after intravenous administration of lipopolysaccharide (LPS). We investigated the effect of treatment with Cygb in POA primary cultures stimulated with LPS for 4 h. The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were measured and the results showed that Cygb reduced the concentrations of both cytokines. We further observed a decrease in immunoreactivity of the inflammatory transcription factor nuclear factor-κB (NF-κB), but not NF-IL6 and STAT3, in the nucleus of Cygb-treated POA cells. These findings suggest that Cygb attenuates the secretion of IL-6 and TNF-α in LPS-stimulated POA primary cultures via inhibition of the NF-κB signaling pathway, indicating that this protein might play an important role in the control of neuroinflammation and fever.

show abstract

Section: Introductionmentioning

confidence: 91%

Section: Preoptic Area Primary Cell Culturesmentioning

confidence: 99%

Cytoglobin Attenuates Neuroinflammation in Lipopolysaccharide-Activated Primary Preoptic Area Cells via NF-κB Pathway Inhibition

Gomes

Sousa

Ott

et al. 2019

Front. Mol. Neurosci.

View full text Add to dashboard Cite

show abstract

“…[11][12][13][14] Emerging evidences indicated that Cygb is negatively associated with liver fibrosis and HCC tumorigenesis via regulating oxidative stress pathways. [15][16][17][18][19] Cygb absence accounts for a high incidence of multiple malignancies including liver, lung and colon cancer and lymphoma in aged Cygb −/− mice, compared with wide-type mice. 20,21 Its deficiency also contributes to tumor recurrence and poor prognosis in human gliomas.…”

Section: The Interaction Of Ons Withmentioning

confidence: 99%

“…It is a dynamic mediator in the maintenance of redox homeostasis and performs the activities of peroxidase and nitric oxide dioxygenase (NOD), which catalyzes nitric oxide (NO) or nitrite to nitrate in rat hepatocytes . Emerging evidences indicated that Cygb is negatively associated with liver fibrosis and HCC tumorigenesis via regulating oxidative stress pathways . Cygb absence accounts for a high incidence of multiple malignancies including liver, lung and colon cancer and lymphoma in aged Cygb −/− mice, compared with wide‐type mice .…”

Section: Introductionmentioning

confidence: 99%

Cytoglobin ameliorates the stemness of hepatocellular carcinoma via coupling oxidative‐nitrosative stress signals

Zhang

Pei

Yang

et al. 2018

Molecular Carcinogenesis

View full text Add to dashboard Cite

Cancer stem cells (CSCs) account for tumor self‐renewal and heterogeneity. Oxidative‐nitrosative stress (ONS) is an independent etiologic factor throughout tumorigenesis. Emerging evidences indicated that the interaction of ONS with CSCs contributes to tumor progression and resistance to chemoradiotherapy. Cytoglobin (Cygb) is a member of human hexacoordinate hemoglobin family and acts as a dynamic mediator of redox homeostasis. We observed that Cygb is significantly deregulated in human hepatocellular carcinoma (HCC) tissue and its decrease aggravates the growth of liver cancer stem cells (LCSCs) and increases the subpopulation of CD133(+) LCSCs. Cygb restoration inhibits HCC proliferation and LCSC growth, and decreases the subpopulation of CD133 (+) LCSCs in vitro. We found that Cygb absence promotes LCSC phenotypes and PI3 K/AKT activation, whereas Cygb restoration inhibits LCSC phenotypes and PI3 K/AKT activation. Furthermore, exogenous antioxidants can eliminate the inhibitory effect of Cygb to LCSC growth and phenotypes, as well as PI3 K/AKT activation. Collectively, this study demonstrated that cytoglobin functions as a tumor suppressor and targets CSCs at an ONS‐dependent manner. Thus, Cygb restoration could be a novel and promising therapeutic strategy against HCC with aberrant ROS/RNS accumulation.

show abstract

“…[19] In the previously study, we found rhCygb had the e cacy of preventing atherosclerosis, protecting against chronic liver disease and liver brosis. [20][21][22][23] Therefore, in this study, we intended to investigate the e cacy of rhCygb in a lung brosis rat model induced with BLM.…”

Section: Introductionmentioning

confidence: 99%

rhCygb reverses bleomycin-induced established pulmonary fibrosis in rats

Zhongshun

Wang

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

PurposeRecombinant human cytoglobin (rhCygb) has been demonstrated to anti-inflammation, anti-oxidation, anti-fibrosis in liver and kidney in animal disease models. However, the effect of rhCygb on the progression of pulmonary fibrosis is still unclear. The aim of this study was to investigate the therapeutic effect of rhCygb in the bleomycin (BLM)-induced pulmonary fibrosis rats.MethodsWe tested whether rhCygb would reverse lung fibrosis (at day 28 and 56) in Sprague-Dawley rats treated with bleomycin. Bleomycin (5mg/kg) resulted in fibrosis by CT and serum measurement at day 7. Effects of rhCygb treatment on morphological and CT imaging of the lung, as well as serial serum levels of biomarkers with progressive lung fibrosis were tested at day 28 and 56.ResultsIn BLM-treated rats (7 days), the well-established lung fibrosis was evidence by changes in rat lungs with CT images and serum levels of hyaluronic acid (HA), laminin (LN), procollagen III N-terminal peptide (PIIINP) and type IV collagen (IVC).After treatment with rhCygb for 49 days, we found significantly decreasing in HA, LN, PIIINP and IVC levels almost to controls. Hydroxyproline (HYP) , CT mean lung density（MLD）and Masson collage volume fraction (CVF) were also significantly reduced. Furthermore, CT MLD positively correlated with serum levels of HA, LN, PIIINP, IVC, and HYP, and especially with CVF.ConclusionrhCygb may be a new potential medicine for reversing lung fibrosis in the future.

show abstract

Protective effects of recombinant human cytoglobin against chronic alcohol-induced liver disease in vivo and in vitro

Cited by 14 publications

References 43 publications

Cytoglobin Attenuates Neuroinflammation in Lipopolysaccharide-Activated Primary Preoptic Area Cells via NF-κB Pathway Inhibition

Cytoglobin Attenuates Neuroinflammation in Lipopolysaccharide-Activated Primary Preoptic Area Cells via NF-κB Pathway Inhibition

Cytoglobin ameliorates the stemness of hepatocellular carcinoma via coupling oxidative‐nitrosative stress signals

rhCygb reverses bleomycin-induced established pulmonary fibrosis in rats

Contact Info

Product

Resources

About