Activation of EphA1-Epha receptor axis attenuates diabetic nephropathy in mice

Li, Yihui; Yan, Hongdan; Wang, Feng; Huang, Shanying; Zhang, Yun; Wang, Wenwen; Zhong, Ming; Zhang, Wei

doi:10.1016/j.bbrc.2017.03.100

Cited by 9 publications

(3 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, our findings include two ligands for Eph-related tyrosine kinases (EFNB1 and EFNB2) and an Eph receptor (EphB6). Eph/ephrin signaling has broad effects and has been implicated in maintenance of the barrier function of the glomerular slit diaphragm (19) and attenuation of renal fibrosis in diabetic nephropathy in mice (20).…”

Section: Discussionmentioning

confidence: 99%

Circulating testican-2 is a podocyte-derived marker of kidney health

Ngo

Wen

Gao

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

In addition to their fundamental role in clearance, the kidneys release select molecules into the circulation, but whether any of these anabolic functions provides insight on kidney health is unknown. Using aptamer-based proteomics, we characterized arterial (A)-to-renal venous (V) gradients for >1,300 proteins in 22 individuals who underwent invasive sampling. Although most of the proteins that changed significantly decreased from A to V, consistent with renal clearance, several were found to increase, the most significant of which was testican-2. To assess the clinical implications of these physiologic findings, we examined proteomic data in the Jackson Heart Study (JHS), an African-American cohort (n = 1,928), with replication in the Framingham Heart Study (FHS), a White cohort (n = 1,621). In both populations, testican-2 had a strong, positive correlation with estimated glomerular filtration rate (eGFR). In addition, higher baseline testican-2 levels were associated with a lower rate of eGFR decline in models adjusted for age, gender, hypertension, type 2 diabetes, body mass index, baseline eGFR, and albuminuria. Glomerular expression of testican-2 in human kidneys was demonstrated by immunohistochemistry, immunofluorescence, and electron microscopy, while single-cell RNA sequencing of human kidneys showed expression of the cognate gene, SPOCK2, exclusively in podocytes. In vitro, testican-2 increased glomerular endothelial tube formation and motility, raising the possibility that its secretion has a functional role within the glomerulus. Taken together, our findings identify testican-2 as a podocyte-derived biomarker of kidney health and prognosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Circulating testican-2 is a podocyte-derived marker of kidney health

Ngo

Wen

Gao

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…In terms of the mechanism of EphA1 with tumor microenvironment, the available cumulative findings demonstrate that EphA1 promotes tumorigenicity and tumor progression in tumor cells and in the tumor microenvironment by binding to the ligand Ephrin and then generating cell contactdependent bidirectional signals. The Eph-Ephrin signaling pathway can regulate cancer cell shape, movement, survival, and proliferation [32], and it may also interact with other signaling systems or trigger a network of signaling processes or downstream mediators to affect malignancy [33,34]. This suggests that the mechanisms of the Eph/Ephrin signaling pathways are complex and need to be further investigated.…”

Section: Clinical Researchmentioning

confidence: 99%

Association Between EphA1 and Tumor Microenvironment in Gastric Carcinoma and its Clinical Significance

Wang

Yin

et al. 2020

Med Sci Monit

View full text Add to dashboard Cite

Departmental sources Background: With the growing global burden of gastric carcinoma (GC) and the urgent need for biomolecular targeted therapies, this study aimed to elucidate the relationship between EphA1 and the tumor microenvironment (focusing primarily on the key inflammatory cytokines IL-6 and tumor angiogenic cytokine VEGF) to identify a new potential therapeutic target. Material/Methods: IHC and qRT-PCR were performed to quantify the protein and gene expression levels of EphA1, IL-6, and VEGF in normal mucosal tissues, carcinoma tissues, and paracarcinomatous tissues from 57 GC patients. Spearman's rank correlation test was performed to determine the relationship between EphA1, IL-6, and VEGF expression levels. The relationships of EphA1 with clinicopathologic parameter and survival in GC patients were also evaluated. Results: The protein and gene expression levels of EphA1 were all attenuated gradually from carcinoma tissues to paracarcinomatous tissues and then to normal mucosal tissues in GC patients. Additionally, significant correlations between the overexpression of EphA1 with aggressive clinicopathological features and shorter survival time of GC patients were verified. In particular, we found a significant positive correlation between the expression of EphA1 and tumor microenvironment hallmark proteins IL-6 and VEGF in carcinoma tissues and paracarcinomatous tissues. Conclusions: EphA1 can promote the occurrence and development of GC by its selective high expression in cancer tissues and its relationship with malignant clinical features and prognosis of GC patients. The underlying potential mechanism appears to involve enhancement of the tumor microenvironment, which via drives the expression of tumor microenvironment hallmark proteins IL-6 and VEGF.

show abstract

“…Among the differential metabolites found in the present study, Indolelactic acid and L-kynurenine were the products of L-tryptophan. The receptors of tyrosine kinases (Eph family) serve as key modulators of various cellular functions [39]: it has been reported that overexpression of EphA1 in the kidney attenuates renal fibrosis and improves renal function by inhibiting Rho and MAPK [40]. As the inhibitor of Rho kinases, Fas may alleviate kidney injury by promoting the expression of EphA1, which in turn activates tyrosine kinases.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics study of fasudil on cisplatin-induced kidney injury

Xia

Lai

et al. 2019

Bioscience Reports

View full text Add to dashboard Cite

Fasudil is a derivative of 5-isoquinoline sulfonamide, which is a Rho kinase inhibitor, a wide range of pharmacological effects. Fasudil has been shown to attenuate kidney injury caused by certain substances. In the present study, metabolomic analysis of mouse kidney tissues ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry was used to determine the metabolomic changes in cisplatin-induced kidney injury and the fasudil-induced attenuation of cisplatin-induced kidney injury. Metabolomic profiling of kidney tissues revealed significant differences in metabolites between the control group and the cisplatin group and between the cisplatin group and the fasudil-intervention group. With metabolomic approach, 68 endogenous differential metabolites were found, and multivariate statistical analysis, accurate molecular weights, isotope tracers, mass-spectrometry secondary-fragment information, and standard-reference comparisons were used to identify these substances. Based on these differential metabolites, a metabolic-pathway network was constructed and revealed that fasudil primarily attenuated cisplatin-induced renal injury by modulating lipid and amino-acid metabolism. These results further demonstrate that kidney injury can be induced by cisplatin and, moreover, suggest that fasudil can be used to reduce kidney injury at early stages in patients treated with cisplatin.

show abstract

Activation of EphA1-Epha receptor axis attenuates diabetic nephropathy in mice

Cited by 9 publications

References 20 publications

Circulating testican-2 is a podocyte-derived marker of kidney health

Circulating testican-2 is a podocyte-derived marker of kidney health

Association Between EphA1 and Tumor Microenvironment in Gastric Carcinoma and its Clinical Significance

Metabolomics study of fasudil on cisplatin-induced kidney injury

Contact Info

Product

Resources

About