title: ELMO1 protects renal structure and ultrafiltration in kidney development and under diabetic conditions.
abstract: 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.
authors.affiliation: Department of Vascular Biology and Tumor Angiogenesis, Center for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Krishna Rakesh
authors.initials: KR
authors.lastname: Sharma
authors.affiliation: Department of Vascular Biology and Tumor Angiogenesis, Center for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Heckler
authors.affiliation: Department of Vascular Biology and Tumor Angiogenesis, Center for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.|Division of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ-ZMBH Alliance), Heidelberg, Germany.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Stoll
authors.affiliation: Department of Pathology and Medical Biology, Division of Pathology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jan-Luuk
authors.initials: JL
authors.lastname: Hillebrands
authors.affiliation: Institute of Pathology, Heidelberg University, Heidelberg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Kynast
authors.affiliation: Institute of Pathology, Heidelberg University, Heidelberg, Germany.|Tissue Bank of the National Center for Tumor Diseases (NCT), Heidelberg, Germany.
authors.forename: Esther
authors.initials: E
authors.lastname: Herpel
authors.affiliation: Institute of Pathology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Porubsky
authors.affiliation: Institue of Neuroanatomy, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Marlies
authors.initials: M
authors.lastname: Elger
authors.affiliation: Department of Urology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Hadaschik
authors.affiliation: Institute of Transfusion Medicine and Immunology and FlowCore Manneim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Bieback
authors.affiliation: Fifth Medical Department, University Medical Centre Mannheim, Mannheim, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hammes
authors.affiliation: Department of Medicine I and Clinical Chemistry, Heidelberg University, Heidelberg, Germany.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Nawroth
authors.affiliation: Department of Vascular Biology and Tumor Angiogenesis, Center for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.|Division of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ-ZMBH Alliance), Heidelberg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Kroll
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D003921:Diabetes Mellitus, Experimental / Q000196:embryology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000196:embryology* / Q000473:pathology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D029961:Zebrafish Proteins