Endothelial Notch activation promotes neutrophil transmigration via downregulating endomucin to aggravate hepatic ischemia/reperfusion injury

Zhang, Peiran; Yue, Kangyi; Liu, Xinli; Yan, Xianchun; Yang, Ziyan; Duan, Jialin; Chen, Xia; Xu, Xinyuan; Zhang, Mei; Liang, Liang; Wang, Lin; Han, Hua

doi:10.1007/s11427-019-1596-4

Cited by 17 publications

(10 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[ 13 ] Chen et al reported that DLL4 regulates LSEC capillarization and fibrogenesis in a CCl 4 ‐induced mouse model of fibrosis. [ 41 ] Meanwhile, Zhang et al found that endothelial Notch activation exacerbates hepatic ischemia–reperfusion injury by contributing to neutrophil transmigration. [ 42 ] Nevertheless, few studies have investigated the changes in Notch signaling in LSECs in NASH.…”

Section: Discussionmentioning

confidence: 99%

Notch‐triggered maladaptation of liver sinusoidal endothelium aggravates nonalcoholic steatohepatitis through endothelial nitric oxide synthase

et al. 2022

Self Cite

View full text Add to dashboard Cite

Background and Aims: Although NASH can lead to severe clinical consequences, including cirrhosis and hepatocellular carcinoma, no effective treatment is currently available for this disease. Increasing evidence indicates that LSECs play a critical role in NASH pathogenesis; however, the mechanisms involved in LSEC-mediated NASH remain to be fully elucidated. Approach and Results:In the current study, we found that LSEC homeostasis was disrupted and LSEC-specific gene profiles were altered in methionine-choline-deficient (MCD) diet-induced NASH mouse models. Importantly, Notch signaling was found to be activated in LSECs of NASH mice. To then investigate the role of endothelial Notch in NASH progression, we generated mouse lines with endothelial-specific Notch intracellular domain (NICD) overexpression or RBP-J knockout to respectively activate or inhibit Notch signaling in endothelial cells. Notably, endothelial-specific overexpression of the NICD accelerated LSEC maladaptation and aggravated NASH, whereas endothelial cell-specific inhibition of Notch signaling restored LSEC homeostasis and improved NASH phenotypes. Furthermore, we demonstrated that endothelial-specific Notch activation exacerbated NASH by inhibiting endothelial nitric oxide synthase (eNOS) transcription, whereas administration of the pharmacological eNOS activator YC-1 alleviated hepatic steatosis and lipid accumulation resulting from Notch activation. Finally, to explore the therapeutic potential of using Notch inhibitors in NASH treatment, we applied two gamma-secretase inhibitors-DAPT and LY3039478-in an

show abstract

Section: Discussionmentioning

confidence: 99%

Notch‐triggered maladaptation of liver sinusoidal endothelium aggravates nonalcoholic steatohepatitis through endothelial nitric oxide synthase

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…BTK has functions on E-selectin dependent neutrophils' slow-rolling by activation of β2-integrins among the PLCγ2 and Phosphoinositide 3-kinase (PI3K) pathway. 9,10 Another role for BTK in neutrophils is inducing the release of granule proteins and reactive oxygen species (ROS). 10 This activity depends on fungal recognition on β-glucan and integrin CR3 adhesion molecules.…”

Section: Introductionmentioning

confidence: 99%

“…9,10 Another role for BTK in neutrophils is inducing the release of granule proteins and reactive oxygen species (ROS). 10 This activity depends on fungal recognition on β-glucan and integrin CR3 adhesion molecules. The adhesions trigger the PI3K pathway and the non-oxidative intracellular mechanism of killing.…”

Section: Introductionmentioning

confidence: 99%

“…The adhesions trigger the PI3K pathway and the non-oxidative intracellular mechanism of killing. 9,10 PI3K signaling pathways are considered as a critical component of the immune response regulation; this has lead researchers to focus on this pathway for more investigations profoundly. PI3K pathway activity is correlated with the promotion of cell growth, survival, and resistance to radiotherapy and chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

<p>An Overview of the Management of the Most Important Invasive Fungal Infections in Patients with Blood Malignancies</p>

Shariati¹,

Moradabadi²,

Chegini³

et al. 2020

IDR

View full text Add to dashboard Cite

In patients with hematologic malignancies due to immune system disorders, especially persistent febrile neutropenia, invasive fungal infections (IFI) occur with high mortality. Aspergillosis, candidiasis, fusariosis, mucormycosis, cryptococcosis and trichosporonosis are the most important infections reported in patients with hematologic malignancies that undergo hematopoietic stem cell transplantation. These infections are caused by opportunistic fungal pathogens that do not cause severe issues in healthy individuals, but in patients with hematologic malignancies lead to disseminated infection with different clinical manifestations. Prophylaxis and creating a safe environment with proper filters and air pressure for patients to avoid contact with the pathogens in the surrounding environment can prevent IFI. Furthermore, due to the absence of specific symptoms in IFI, rapid and accurate diagnosis reduces the mortality rate of these infections and using molecular techniques along with standard mycological methods will improve the diagnosis of disseminated fungal infection in patients with hematologic disorders. Amphotericin B products, extended-spectrum azoles, and echinocandins are the essential drugs to control invasive fungal infections in patients with hematologic malignancies, and according to various conditions of patients, different results of treatment with these drugs have been reported in different studies. On the other hand, drug resistance in recent years has led to therapeutic failures and deaths in patients with blood malignancies, which indicates the need for antifungal susceptibility tests to use appropriate therapies. Life-threatening fungal infections have become more prevalent in patients with hematologic malignancies in recent years due to the emergence of new risk factors, new species, and increased drug resistance. Therefore, in this review, we discuss the different dimensions of the most critical invasive fungal infections in patients with hematologic malignancies and present a list of these infections with different clinical manifestations, treatment, and outcomes.

show abstract

“…Functionally, knocking down endomucin does not affect the migration of adenoma cells in vitro 29 . Recently, Zhang et al showed that endothelial Notch signaling controls neutrophil trans‐migration via endomucin to modulate acute inflammation in hepatic ischemia reperfusion injury 30 …”

Section: Other Functions Of Endomucinmentioning

confidence: 99%

Research progress on the structure and function of endomucin

Zhang

Yang

Gao

2020

Anim Models and Exp Med

View full text Add to dashboard Cite

Endomucin is a type I integral membrane glycoprotein, which is expressed in venous and capillary endothelial cells. It consists of 261 amino acids with an extracellular domain that is highly O‐glycosylated at serine and threonine residues and has several potential N‐glycosylation sites. Endomucin plays an important role in biological processes such as cell interaction, molecular cell signaling, angiogenesis and cell migration, and in recent years it has also been identified as an anti‐adhesion molecule and a marker of endothelial cells. While it has been shown to be involved in a number of physiological and pathological mechanisms, many of its functions remain unknown, and further study is needed. This article reviews research progress on the function of endomucin to date, in order to provide guidance for future studies.

show abstract

Endothelial Notch activation promotes neutrophil transmigration via downregulating endomucin to aggravate hepatic ischemia/reperfusion injury

Cited by 17 publications

References 51 publications

Notch‐triggered maladaptation of liver sinusoidal endothelium aggravates nonalcoholic steatohepatitis through endothelial nitric oxide synthase

Notch‐triggered maladaptation of liver sinusoidal endothelium aggravates nonalcoholic steatohepatitis through endothelial nitric oxide synthase

<p>An Overview of the Management of the Most Important Invasive Fungal Infections in Patients with Blood Malignancies</p>

Research progress on the structure and function of endomucin

Contact Info

Product

Resources

About