Identification of Basp1 as a novel angiogenesis‐regulating gene by multi‐model system studies

Khajavi, Mehrdad; Zhou, Yi; Schiffer, Alex; Bazinet, Lauren; Birsner, Amy E.; Zon, Leonard I.; D’Amato, Robert J.

doi:10.1096/fj.202001936rrr

Cited by 7 publications

(7 citation statements)

References 44 publications

(103 reference statements)

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“…In addition to EGFR signaling, Wnt/β‐catenin and Dll4/Notch1 signaling pathways are also abnormally activated in high glucose‐treated endothelial cells and contribute to diabetic endothelial dysfunction 29 , 30 , 31 . Herein, silencing of BASP1 was found to be effective in inhibiting Wnt/β‐catenin and Dll4/Notch1 signaling pathways, which was in line with a previously reported article 42 . It seems that BAPS1 regulates various signaling pathways in diabetic endothelial dysfunction.…”

Section: Discussionsupporting

confidence: 90%

BASP1 promotes high glucose‐induced endothelial apoptosis in diabetes via activation of EGFR signaling

Sun

Liu

Wang

et al. 2023

J of Diabetes Invest

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Aims Diabetes mellitus is a common chronic disease of glucose metabolism. Endothelial dysfunction is an early event in diabetes complicated by cardiovascular disease. This study aimed to reveal the expression of BASP1 and its biological roles in endothelial cell dysfunction in diabetes complicated by cardiovascular disease. Materials and Methods By analyzing the databases related to diabetes complicated with coronary heart disease, BASP1 was screened out as an upregulated gene. Human umbilical vein endothelial cells (HUVECs) and primary mouse aortic endothelial cells were treated with high glucose to establish cell models of diabetes‐related endothelial dysfunction, and the expression changes of BASP1 were verified by RT‐qPCR, western blot, and immunofluorescence. BASP1 was silenced or overexpressed by siRNA or overexpression plasmid, and its effects on cell migration, apoptosis, tube formation, inflammatory response, and ROS were detected. The possible signaling pathway of BASP1 was found and the mechanism of BASP1 on promoting the progression of endothelial dysfunction was explored using the EGFR inhibitor, gefitinib. Results Bioinformatics analysis indicated that the expression of BASP1 in patients with diabetes mellitus and concomitant coronary heart disease was increased. High glucose induced the upregulation of BASP1 expression in endothelial cells, and showed a time‐dependent relationship. Silencing of BASP1 alleviated the damage of high glucose to endothelial cells. BASP1 regulated EGFR positively. The promoting effect of BASP1 on endothelial cell apoptosis may be achieved by regulating the EGFR pathway. Conclusion BASP1 promotes endothelial cell injury induced by high glucose in patients with diabetes, which may be activated by activating the EGFR pathway.

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Section: Discussionsupporting

confidence: 90%

BASP1 promotes high glucose‐induced endothelial apoptosis in diabetes via activation of EGFR signaling

Sun

Liu

Wang

et al. 2023

J of Diabetes Invest

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“…On the basis of our initial observations of increased angiogenesis in Dusp3 −/− kidneys, we first focused on the phosphorylation sites of pro‐angiogenic factors. As summarized in Table 1, we found an increased phosphorylation of BASP1 and DLG1, which are well‐established promoters of angiogenesis via the β‐catenin and Dll4/Notch1 signalling pathways 21,22 . Most of the pro‐angiogenetic factors found with increased phosphorylation levels in Dusp3 −/− vs WT ischaemic kidneys are involved in VEGF‐mediated signalling: EPS8, FARP1, DOCK1, ARHGEF17, FARP2, IQGAP1, YY1, SIRT2, ARHGAP17, NDRG1 23–29 .…”

Section: Resultsmentioning

confidence: 68%

“…in Table 1, we found an increased phosphorylation of BASP1 and DLG1, which are well-established promoters of angiogenesis via the β-catenin and Dll4/Notch1 signalling pathways. 21,22 Most of the pro-angiogenetic factors found with increased phosphorylation levels in Dusp3 −/− vs WT ischaemic kidneys are involved in VEGF-mediated signalling: EPS8, FARP1, DOCK1, ARHGEF17, FARP2, IQGAP1, YY1, SIRT2, ARHGAP17, NDRG1. [23][24][25][26][27][28][29] Our phosphoproteomics-based observations suggest that the genetic inactivation of Dusp3 may promote angiogenesis via the VEGF signalling pathway, which may in turn increase the vascular density and attenuate the I/R damage.…”

Section: Phosphoproteomics Indicate a Down-regulation Of Inflammatory...mentioning

confidence: 99%

The genetic deletion of the Dual Specificity Phosphatase 3 (DUSP3) attenuates kidney damage and inflammation following ischaemia/reperfusion injury in mouse

et al. 2021

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Aim: Dual Specificity Phosphatase 3 (DUSP3) regulates the innate immune response, with a putative role in angiogenesis. Modulating inflammation and perfusion contributes to renal conditioning against ischaemia/reperfusion (I/R). We postulate that the functional loss of DUSP3 is associated with kidney resistance to I/R. Methods: Ten C57BL/6 male WT and Dusp3 −/− mice underwent right nephrectomy and left renal I/R (30 min/48 hours). Renal injury was assessed based on serum levels of urea (BUN) and Jablonski score. The expression of CD31 and VEGF vascular markers was quantified by RT-qPCR and immuno-staining. Renal resistivity index (RRI) was measured in vivo by Doppler ultrasound. Comparative phosphoproteomics was conducted using IMAC enrichment of phosphopeptides. Inflammatory markers were quantified at both mRNA and protein levels in ischaemic vs non-ischaemic kidneys in WT vs Dusp3 −/− . Results: At baseline, we located DUSP3 in renal glomeruli and endothelial cells. CD31-positive vascular network was significantly larger in Dusp3 −/− kidneys compared to WT, with a lower RRI in Dusp3 −/− mice. Following I/R, BUN and Jablonski score were significantly lower in Dusp3 −/− vs WT mice. Phosphoproteomics highlighted a down-regulation of inflammatory pathways and up-regulation of phospho-sites involved in cell metabolism and VEGF-related See editorial article: Ivy J.R. 2022 Does renal ischaemia/reperfusion injury bite the DUSP3? Acta Physiol (Oxf). e13763.

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“… 21 BASP1 is a cofactor of WT1 , and genes in the cholesterol biosynthesis and lipid transport pathways are direct targets of WT1 . 22 The hub proteins identified in this study are S100A8, S100A9, LCN2, and ANXA3.…”

Section: Discussionmentioning

confidence: 70%

Proteomic Analysis of Meibomian Gland Secretions in Patients With Blepharokeratoconjunctivitis

Lin

et al. 2022

Trans. Vis. Sci. Tech.

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Purpose To screen and compare the differential proteins in meibomian gland secretions between patients with blepharokeratoconjunctivitis (BKC) and healthy individuals and to identify target proteins that may participate in the occurrence and development of BKC. Methods Thirteen patients diagnosed with BKC in Shenzhen Eye Hospital and five healthy volunteers were included in this study. Meibomian gland secretions and clinical traits were collected before and after 1 month of standard BKC treatment. Label-free mass spectrometry was used for proteomic detection of meibomian gland secretions. Weighted protein coexpression network analysis (WPCNA) and several different protein analyses were performed to identify hub proteins associated with BKC and its clinical characteristics. Results Patients with BKC had significantly lower cleanliness of the eyelid margin, higher palpebral margin scores, more serious clinical manifestations of secretions, and more damaged meibomian gland morphology compared with the healthy controls. One hundred fifteen differential proteins were associated with the clinical traits, which included diagnosis, sex, age, severity, corneal neovascularization, disease course, eyelid margin cleanliness, palpebral margin score, secretion characteristics, and meibomian gland morphology. Four hub proteins related to inflammation and the immune response (namely, S100A8, S100A9, ANXA3, and LCN2) were increased in BKC and remained increased after 1 month of treatment. The cleanliness, blepharon eyelid score, and secretion characteristics were improved after BKC treatment. Conclusions S100A8, S100A9, ANXA3, and LCN2 are BKC-associated proteins probably involved in the chronic inflammation of BKC. Translational Relevance Hub proteins probably involved in chronic inflammation of BKC were identified by proteomic methods.

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Identification of Basp1 as a novel angiogenesis‐regulating gene by multi‐model system studies

Cited by 7 publications

References 44 publications

BASP1 promotes high glucose‐induced endothelial apoptosis in diabetes via activation of EGFR signaling

BASP1 promotes high glucose‐induced endothelial apoptosis in diabetes via activation of EGFR signaling

The genetic deletion of the Dual Specificity Phosphatase 3 (DUSP3) attenuates kidney damage and inflammation following ischaemia/reperfusion injury in mouse

Proteomic Analysis of Meibomian Gland Secretions in Patients With Blepharokeratoconjunctivitis

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