Activated mesangial cells induce glomerular endothelial cells proliferation in rat anti‐Thy‐1 nephritis through VEGFA/VEGFR2 and Angpt2/Tie2 pathway

Zhao, Yinghua; Fu, Bo; Chen, Pu; Li, Qinggang; Ouyang, Qing; Zhang, Chuyue; Cai, Guangyan; Wu, Lingling; Chen, Xiangmei

doi:10.1111/cpr.13055

Cited by 11 publications

(12 citation statements)

References 60 publications

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“…Increased Angp2 inhibited Tie2 phosphorylation and enhancing Tie2 phosphorylation by Vasculotide alleviated endothelial cell proliferation on day 7 of the anti-Thy1 model. This was suggested as a strategy to lessen the vascular lesions in MPGN ( 178 ).…”

Section: Mesangial-endothelial Crosstalkmentioning

confidence: 99%

The Glomerulus According to the Mesangium

2022

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The glomerulus is the functional unit for filtration of blood and formation of primary urine. This intricate structure is composed of the endothelium with its glycocalyx facing the blood, the glomerular basement membrane and the podocytes facing the urinary space of Bowman's capsule. The mesangial cells are the central hub connecting and supporting all these structures. The components as a unit ensure a high permselectivity hindering large plasma proteins from passing into the urine while readily filtering water and small solutes. There has been a long-standing interest and discussion regarding the functional contribution of the different cellular components but the mesangial cells have been somewhat overlooked in this context. The mesangium is situated in close proximity to all other cellular components of the glomerulus and should be considered important in pathophysiological events leading to glomerular disease. This review will highlight the role of the mesangium in both glomerular function and intra-glomerular crosstalk. It also aims to explain the role of the mesangium as a central component involved in disease onset and progression as well as signaling to maintain the functions of other glomerular cells to uphold permselectivity and glomerular health.

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Section: Mesangial-endothelial Crosstalkmentioning

confidence: 99%

The Glomerulus According to the Mesangium

2022

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“… 32 Existing studies have confirmed that the VEGF‐A/VEGFR signaling pathway is critical for glomerular development and renal homeostasis. 33 , 34 …”

Section: Cross Talk Between Glomerulus Cellsmentioning

confidence: 99%

“…VEGF‐A induces intracellular signaling by binding to one of two receptors: VEGFR‐1 (or Flt‐1) and VEGFR‐2 (or Flk‐1/KDR), and VEGFR‐2 mediates most of the biological effects of VEGF‐A under usual conditions 32 . Existing studies have confirmed that the VEGF‐A/VEGFR signaling pathway is critical for glomerular development and renal homeostasis 33,34 …”

Section: Cross Talk Between Glomerulus Cellsmentioning

confidence: 99%

“…32 Existing studies have confirmed that the VEGF-A/VEGFR signaling pathway is critical for glomerular development and renal homeostasis. 33,34 VEGF-A is expressed predominantly by podocytes during glomerular development, while GEnCs and cortical and reno medullary interstitial fibroblasts express the VEGF receptors. 35 In the glomerulus, the canonical VEGF signaling is the secretion of VEGF-A by podocytes which then crosses the filtration barrier in opposition to urinary and acts by binding to VEGFR-2 on the surface of GEnCs, 36 forming the VEGF-A/VEGFR axis.…”

Section: Vascular Endothelial Growth Factor a Signalingmentioning

confidence: 99%

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Glomerular cell cross talk in diabetic kidney diseases

Dong

2022

Journal of Diabetes

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Diabetic kidney disease (DKD) is a severe microvascular complication of diabetes mellitus. It is the leading inducement of end‐stage renal disease (ESRD), and its global incidence has been increasing at an alarming rate. The strict control of blood pressure and blood glucose can delay the progression of DKD, but intensive treatment is challenging to maintain. Studies to date have failed to find a complete cure. The glomerulus's alterations and injuries play a pivotal role in the initiation and development of DKD. A wealth of data indicates that the interdependent relationship between resident cells in the glomerulus will provide clues to the mechanism of DKD and new ways for therapeutic intervention. This review summarizes the significant findings of glomerular cell cross talk in DKD, focusing on cellular signaling pathways, regulators, and potential novel avenues for treating progressive DKD.

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“…As an early autocrine initiator of angiogenesis, ANGPT2 first destabilizes resting blood vessels, thus allowing VEGF to drive the proliferation and chemotactic migration of vascular buds. ANGPT2 also activates TIE2-expressing monocytes/macrophages (TEM), which promote angiogenesis, tumor formation, metastasis, and immunosuppression ( 26 ). ANGPT2 regulates vascular remodeling and tumor progression under many pathological conditions through different effects on TIE2 signaling.…”

Section: Introductionmentioning

confidence: 99%

Immunoregulation and clinical significance of neutrophils/NETs-ANGPT2 in tumor microenvironment of gastric cancer

Yang

Zou

et al. 2022

Front. Immunol.

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Although significant progress has been made in the study of gastric cancer (GC), clinicians lack reliable protein markers for accurate diagnosis and tumor stratification. Neutrophil extracellular traps (NETs) are networks of extracellular fibers composed of DNA from neutrophils. We have previously reported that abundant NETs are deposited in GC, damaging human umbilical vein endothelial cells (HUVECs) and triggering the release of tissue factors, leading to a hypercoagulable state in GC. However, the specific effects of NETs on HUVECs are unclear. We aimed to explore the functional changes caused by NETs on HUVECs, providing evidence that NETs may fuel GC progression. Through quantitative proteomics, we identified 6182 differentially expressed proteins in NET-stimulated HUVECs by TMT. The reliability of the TMT technique was confirmed by parallel reaction monitoring (PRM) analysis of 17 differentially expressed proteins. Through bioinformatics analysis, we found that NETs upregulate ANGPT2 in HUVECs. We comprehensively analyzed the prognosis, biological function, immune response, and therapeutic value of ANGPT2 in GC. We found that overexpression of ANGPT2 in GC is associated with poor prognosis and potentially regulates multiple biological functions. At the same time, ANGPT2 also predicted immunotherapeutic and chemotherapeutic responses in GC. In conclusion, NETs promoted ANGPT2 overexpression in the GC microenvironment. In the future, the neutrophil/NETs-ANGPT2 axis may provide a new target for the treatment of GC.

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Activated mesangial cells induce glomerular endothelial cells proliferation in rat anti‐Thy‐1 nephritis through VEGFA/VEGFR2 and Angpt2/Tie2 pathway

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 11 publications

References 60 publications

The Glomerulus According to the Mesangium

The Glomerulus According to the Mesangium

Glomerular cell cross talk in diabetic kidney diseases

Immunoregulation and clinical significance of neutrophils/NETs-ANGPT2 in tumor microenvironment of gastric cancer

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