Glomerular mesangial cell recruitment and function require the co-receptor neuropilin-1
| العنوان: | Glomerular mesangial cell recruitment and function require the co-receptor neuropilin-1 |
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| المؤلفون: | Yashpal S. Kanwar, Monika L Wnuk, Isabel Anna Carota, Christina S. Bartlett, Rizaldy P. Scott, Jeffrey H. Miner, Susan E. Quaggin |
| المصدر: | American Journal of Physiology-Renal Physiology. 313:F1232-F1242 |
| بيانات النشر: | American Physiological Society, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.medical_specialty, Time Factors, Co-receptor, Physiology, Glomerular Mesangial Cell, Biology, Transfection, 03 medical and health sciences, Glomerulonephritis, Cell Movement, Internal medicine, Neuropilin 1, medicine, Neuropilin, Animals, Humans, Genetic Predisposition to Disease, Renal Insufficiency, Phosphorylation, Receptor, Cells, Cultured, Mice, Knockout, Proteinuria, Glomerulosclerosis, Proto-Oncogene Proteins c-sis, medicine.disease, Neuropilin-1, Transmembrane protein, Crk-Associated Substrate Protein, Phenotype, 030104 developmental biology, Endocrinology, Mesangial Cells, Disease Progression, RNA Interference, medicine.symptom, Glomerular Filtration Rate, Signal Transduction, Research Article |
| الوصف: | Proteinuria has been reported in cancer patients receiving agents that target the transmembrane receptor neuropilin-1 (Nrp1) suggesting potential adverse effects on glomerular function. Here we show that Nrp1 is highly expressed by mesangial cells and that genetic deletion of the Nrp1 gene from PDGF receptor-β+mesangial cells results in proteinuric disease and glomerulosclerosis, leading to renal failure and death within 6 wk of age in mice. The major defect is a failure of mesangial cell migration that is required to establish the mature glomerular tuft. In vitro data show that the potent chemotactic effect of PDGFB is lost in Nrp1-deficient mesangial cells. Biochemical analyses reveal that Nrp1 is required for PDGFB-dependent phosphorylation of p130 Crk-associated substrate (p130Cas), a large-scaffold molecule that is involved in motility of other cell types. In stark contrast, matrix adhesion and activation of ERK and Akt, which mediate proliferation of mesangial cells in response to PDGFB, are unaffected by the absence of Nrp1. Taken together, these results identify a critical cell-autonomous role for Nrp1 in the migratory behavior of mesangial cells and may help explain the renal effects that occur in patients receiving Nrp1-inhibitory drugs. |
| تدمد: | 1522-1466 1931-857X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::800daaa7e86cfdbf1214cf328f67a895Test https://doi.org/10.1152/ajprenal.00311.2017Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....800daaa7e86cfdbf1214cf328f67a895 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221466 1931857X |
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