NLRX1 does not play a role in diabetes nor the development of diabetic nephropathy induced by multiple low doses of streptozotocin

Diabetic nephropathy (DN) is a microvascular complication of diabetes mellitus that results in both tubular and glomerular injury. Low-grade inflammation and oxidative stress are two mechanisms known to drive the progression of DN. Nucleotide-binding leucine-rich repeat containing family member X1 (...

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Veröffentlicht in:	PloS one Jg. 14; H. 3; S. e0214437
Hauptverfasser:	Scantlebery, Angelique M. L., Uil, Melissa, Butter, Loes M., Poelman, Renée, Claessen, Nike, Girardin, Stephen E., Florquin, Sandrine, Roelofs, Joris J. T. H., Leemans, Jaklien C.
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States Public Library of Science 25.03.2019 Public Library of Science (PLoS)
Schlagworte:	Animals Antioxidants Authorship Biology and Life Sciences Body weight Body weight loss Butter Cellular stress response Diabetes Diabetes mellitus Diabetes mellitus (insulin dependent) Diabetes Mellitus, Experimental - metabolism Diabetes Mellitus, Experimental - pathology Diabetic nephropathies Diabetic Nephropathies - metabolism Diabetic Nephropathies - pathology Diabetic nephropathy Dose-Response Relationship, Drug Fibrosis Glucose Hemoglobin Hyperglycemia Inflammation Kidney - drug effects Kidney - metabolism Kidney - pathology Kidney diseases Kidneys Leucine Male Medicine and Health Sciences Metabolism Mice Mice, Inbred C57BL Microvasculature Mitochondria Mitochondrial Proteins - deficiency Mitochondrial Proteins - metabolism Nephropathy Oxidative phosphorylation Oxidative stress Oxidative Stress - drug effects Pathogenesis Pathology Phenotype Phenotypes Phosphorylation Physiological effects Polydipsia Polyuria Proteins Streptozocin Streptozocin - pharmacology Tumor necrosis factor-TNF Type 1 diabetes Urination disorders Weight loss Netherlands
ISSN:	1932-6203, 1932-6203
Online-Zugang:	Volltext
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Zusammenfassung:	Diabetic nephropathy (DN) is a microvascular complication of diabetes mellitus that results in both tubular and glomerular injury. Low-grade inflammation and oxidative stress are two mechanisms known to drive the progression of DN. Nucleotide-binding leucine-rich repeat containing family member X1 (NLRX1) is an innate immune receptor, uniquely located in mitochondria, that has been found to regulate inflammatory responses and to dampen renal oxidative stress by regulating oxidative phosphorylation. For this reason, we investigated the role of NLRX1 in the development of DN in a Type 1 Diabetes mouse model. We analyzed the effect of NLRX1 deficiency on diabetes development and the accompanied renal damage, inflammation, and fibrosis. We found that multiple low doses of streptozotocin induced body weight loss, polydipsia, hyperglycemia, glycosuria, and a mild DN phenotype in wildtype and NLRX1-deficient mice, without significant differences between these mouse strains. Despite increased NLRX1 expression in diabetic wildtype mice, NLRX1 deficiency did not affect the diabetic phenotype induced by streptozotocin treatment, as reflected by similar levels of polyuria, microalbuminuria, and increased renal markers of oxidative stress and inflammation in wildtype and NLRX1-deficient mice. The present findings show that NLRX1 does not mediate the development of streptozotocin-induced diabetes and diabetic-induced nephropathy in mice after multiple low doses of streptozotocin. This data implies that, while NLRX1 can be triggered by cellular stress, its regulatory and functional effects may be dependent on the specific physiological conditions. In the case of DN, NLRX1 may be neither helpful nor harmful, but rather a marker of metabolic stress.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 LMB, RP, NC also contributed equally to this work and JR and JL share last authorship. Competing Interests: The authors have declared that no competing interests exist.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0214437