ELMO1 protects renal structure and ultrafiltration in kidney development and under diabetic conditions
| العنوان: | ELMO1 protects renal structure and ultrafiltration in kidney development and under diabetic conditions |
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| المؤلفون: | Stefan Porubsky, Katharina L. Kynast, Krishna Rakesh Sharma, HP Hammes, Sandra J. Stoll, Peter P. Nawroth, Boris Hadaschik, Karen Bieback, Esther Herpel, Jens Kroll, Marlies Elger, Jan-Luuk Hillebrands, Karl Heckler |
| المساهمون: | Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), Groningen Institute for Organ Transplantation (GIOT) |
| المصدر: | Scientific Reports Scientific Reports, 6:37172. Nature Publishing Group |
| بيانات النشر: | Nature Publishing Group, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.medical_specialty, GENETICS, NEPHROPATHY, MIGRATION, MODELS, Kidney development, Apoptosis, Kidney, Article, Nephropathy, Diabetes Mellitus, Experimental, Diabetic nephropathy, PATHWAY, Animals, Genetically Modified, 03 medical and health sciences, Internal medicine, PODOCYTE APOPTOSIS, medicine, Animals, Humans, Zebrafish, Adaptor Proteins, Signal Transducing, COMPLICATIONS, Multidisciplinary, biology, Zebrafish Proteins, medicine.disease, biology.organism_classification, VASCULAR MORPHOGENESIS, Pronephros, 030104 developmental biology, Endocrinology, ELMO1, medicine.anatomical_structure, Renal pathology |
| الوصف: | Engulfment and cell motility 1 (ELMO1) functions as a guanine exchange factor for Rac1 and was recently found to protect endothelial cells from apoptosis. Genome wide association studies suggest that polymorphisms within human elmo1 act as a potential contributing factor for the development of diabetic nephropathy. Yet, the function of ELMO1 with respect to the glomerulus and how this protein contributes to renal pathology was unknown. Thus, this study aimed to identify the role played by ELMO1 in renal development in zebrafish, under hyperglycaemic conditions, and in diabetic nephropathy patients. In zebrafish, hyperglycaemia did not alter renal ELMO1 expression. However, hyperglycaemia leads to pathophysiological and functional alterations within the pronephros, which could be rescued via ELMO1 overexpression. Zebrafish ELMO1 crispants exhibited a renal pathophysiology due to increased apoptosis which could be rescued by the inhibition of apoptosis. In human samples, immunohistochemical staining of ELMO1 in nondiabetic, diabetic and polycystic kidneys localized ELMO1 in glomerular podocytes and in the tubules. However, ELMO1 was not specifically or distinctly regulated under either one of the disease conditions. Collectively, these results highlight ELMO1 as an important factor for glomerular protection and renal cell survival via decreasing apoptosis, especially under diabetic conditions. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e9deb33de2de67cf2ba4b6cce3492bb9Test http://europepmc.org/articles/PMC5111104Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e9deb33de2de67cf2ba4b6cce3492bb9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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