| Title |
Slit2/Robo1 signaling is involved in angiogenesis of glomerular endothelial cells exposed to a diabetic-like environment
|
|---|---|
| Published in |
Angiogenesis, January 2018
|
| DOI | 10.1007/s10456-017-9592-3 |
| Pubmed ID | |
| Authors |
Junhui Liu, Weiping Hou, Tao Guan, Luyao Tang, Xufei Zhu, Yi Li, Shihui Hou, Jun Zhang, Hua Chen, Yunjian Huang |
| Abstract |
Abnormal angiogenesis plays a pathological role in diabetic nephropathy (DN), contributing to glomerular hypertrophy and microalbuminuria. Slit2/Robo1 signaling participates in angiogenesis in some pathological contexts, but whether it is involved in glomerular abnormal angiogenesis of early DN is unclear. The present study evaluated the effects of Slit2/Robo1 signaling pathway on angiogenesis of human renal glomerular endothelial cells (HRGECs) exposed to a diabetic-like environment or recombinant Slit2-N. To remove the effect of Slit2 derived from mesangial cells, human renal mesangial cells (HRMCs) grown in high glucose (HG) medium (33 mM) were transfected with Slit2 siRNA and then the HG-HRMCs-CM with Slit2 depletion was collected after 48 h. HRGECs were cultured in the HG-HRMCs-CM or recombinant Slit2-N for 0, 6, 12, 24, or 48 h. The mRNA and protein expressions of Slit2/Robo1, PI3K/Akt and HIF-1α/VEGF signaling pathways were detected by quantitative real-time PCR, western blotting, and ELISA, respectively. The CCK-8 cell proliferation assay, flow cytometry and the scratch wound-healing assay were used to assess cell proliferation, cycles, and migration, respectively. Matrigel was used to perform a tubule formation assay. Our results showed that the HG-HRMCs-CM with Slit2 depletion enhanced the activation of Slit2/Robo1, PI3K/Akt, and HIF-1α/VEGF signaling in HRGECs in time-dependent manner (0-24 h post-treatment). In addition, the HG-HRMCs-CM with Slit2 depletion significantly promoted HRGECs proliferation, migration, and tube formation. Pretreatment of HRGECs with Robo1 siRNA suppressed the activation of PI3K/Akt and HIF-1α/VEGF signaling and inhibited angiogenesis, whereas PI3K inhibitor suppressed HIF-1α/VEGF signaling, without influencing Robo1 expression. In the HRGECs treated with Slit2-N, Slit2-N time-dependently enhanced the activation of Robo1/PI3K/Akt/VEGF pathway but not HIF-1α activity, and promoted HRGECs proliferation, migration, and tube formation. The effects induced by Slit2 were also abolished by Robo1 siRNA and PI3K inhibitor. Taken together, our findings indicate that in a diabetic-like environment, in addition to mesangial cells, autocrine activation of Slit2/Robo1 signaling of HRGECs may contribute to angiogenesis of HRGECs through PI3K/Akt/VEGF pathway; therefore, Slit2/Robo1 signaling may be a potent therapeutic target for the treatment of abnormal angiogenesis in early DN and may have broad implications for the treatment of other diseases dependent on pathologic angiogenesis. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 16 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 3 | 19% |
| Student > Ph. D. Student | 3 | 19% |
| Student > Bachelor | 2 | 13% |
| Other | 1 | 6% |
| Unspecified | 1 | 6% |
| Other | 2 | 13% |
| Unknown | 4 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 5 | 31% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 13% |
| Veterinary Science and Veterinary Medicine | 1 | 6% |
| Unspecified | 1 | 6% |
| Immunology and Microbiology | 1 | 6% |
| Other | 2 | 13% |
| Unknown | 4 | 25% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 20 January 2018.
All research outputs
#17,925,346
of 23,015,156 outputs
Outputs from Angiogenesis
#383
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Outputs of similar age
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Outputs of similar age from Angiogenesis
#9
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