<i>GSTM1</i> Deletion Exaggerates Kidney Injury in Experimental Mouse Models and Confers the Protective Effect of Cruciferous Vegetables in Mice and Humans
Gigliotti JC, Tin A, Pourafshar S, Cechova S, Wang YT, Sung SJ, Bodonyi-Kovacs G, Cross JV, Yang G, Nguyen N, Chan F, Rebholz C, Yu B, Grove ML, Grams ME, Köttgen A, Scharpf R, Ruiz P, Boerwinkle E, Coresh J, Le TH
Journal of the American Society of Nephrology : JASN · 33 citas
Cómo se estudió
- Diseño
- Estudio en animales (clasificado por nuestro filtro de IA)
- Estudiado en
- Personas, más trabajo en animales o laboratorio
- Resultado principal
- Eventos clínicos como enfermedad o muerte
- Consumo medido con
- No se indica
Quién lo pagó
- Financiación
- Financiación independiente
- Gobierno
- Deutsche Forschungsgemeinschaft
- Gobierno
- National Institutes of Health
- Gobierno
- National Heart, Lung, and Blood Institute
- Gobierno
- National Institute of Diabetes and Digestive and Kidney Diseases
- Gobierno
- National Center for Research Resources
- Gobierno
- NHLBI NIH HHS
- Gobierno
- NIDDK NIH HHS
- Gobierno
- German Research Foundation
- Gobierno
- NCRR NIH HHS
- Universidad u hospital
- Coordinated Research Center
- Subvenciones
- National Heart, Lung, and Blood Institute (HHSN268201 100012C); National Heart, Lung, and Blood Institute (HHSN268201100007I); National Heart, Lung, and Blood Institute (HHSN268201100007C); National Heart, Lung, and Blood Institute (HHSN2682 01100008C); National Heart, Lung, and Blood Institute (HH-SN-268201100006C); National Heart, Lung, and Blood Institute (HHSN268201100011C); National Institute of Diabetes and Digestive and Kidney Diseases (T32 DK072922); National Heart, Lung, and Blood Institute (HHSN2682011-00005I); National Heart, Lung, and Blood Institute (HHSN2682011-00009I); National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK094907); National Center for Research Resources (S10 RR026799); National Heart, Lung, and Blood Institute (HHSN268201100005C); National Heart, Lung, and Blood Institute (HHSN268201100005G); National Heart, Lung, and Blood Institute (HHSN268201100010C); Deutsche Forschungsgemeinschaft (KO 3598/3-1); National Heart, Lung, and Blood Institute (HHSN268201100011I); National Heart, Lung, and Blood Institute (HHSN26820 1100009C); National Heart, Lung, and Blood Institute (HHSN2682011-00008I); National Institute of Diabetes and Digestive and Kidney Diseases (R21 DK112087); National Heart, Lung, and Blood Institute (R21 HL098941); National Institutes of Health (R21HL098941)
Según 10 financiadores declarados.
Publicación
- Publicado
- 2019-11-14 · J Am Soc Nephrol · vol. 31 · número 1 · págs. 102–116
- Editorial
- American Society of Nephrology
- Citado
- 45 citas · más que el 83% de estudios similares · 1.5× el promedio de su campo
- Referencias
- 57 trabajos
- Acceso
- Acceso abierto (copia en repositorio)
- Áreas de investigación
- Glutathione Transferases and Polymorphisms · Genomics, phytochemicals, and oxidative stress · Endometriosis Research and Treatment
- Palabras clave
- Kidney disease, Kidney, Medicine, Knockout mouse, Cruciferous vegetables, Internal medicine, Inflammation, Oxidative stress, Endocrinology, Nephropathy, Disease, Physiology, Immunology, Biology, Cancer, Diabetes mellitus, Receptor
- MeSH
- animals, humans, mice, brassicaceae, vegetables, disease models, animal, glutathione transferase, diet, gene deletion, middle aged, female, male, renal insufficiency, chronic
21 autores
- Joseph Christopher Gigliotti🇺🇸Liberty University
- Adrienne Tin🇺🇸Welch Foundation
- Shirin Pourafshar
- Sylvia Cechova
- Yves T. Wang🇺🇸University of Rochester
- Sun‐Sang J. Sung
- Gabor Bodonyi-Kovacs
- Janet V. Cross🇺🇸University of Virginia
- Guang Yang🇩🇪Heinrich Heine University Düsseldorf
- Nhu Nguyen🇺🇸Grand Valley State University
- Fang Chan
- Casey M. Rebholz🇺🇸Welch Foundation
- Bing Yu🇨🇲Health and Human Development (2HD) Research Network
- Megan L. Grove🇺🇸The University of Texas Health Science Center at Houston
- Morgan Erika Grams🇺🇸Welch Foundation
- Anna Köttgen🇩🇪University of Freiburg
- Robert B. Scharpf🇺🇸Johns Hopkins University
- Phillip Ruiz🇺🇸University of Miami
- Eric Boerwinkle🇺🇸The University of Texas Health Science Center at Houston
- Josef Coresh🇺🇸Welch Foundation
- Thu H. Le🇺🇸 · autor de correspondenciaJohns Hopkins University; University of Rochester
Resumen
El texto original del estudio, en el idioma en que se publicó.
Background
GSTM1 encodes glutathione S-transferase μ-1 (GSTM1), which belongs to a superfamily of phase 2 antioxidant enzymes. The highly prevalent GSTM1 deletion variant is associated with kidney disease progression in human cohorts: the African American Study of Kidney Disease and Hypertension and the Atherosclerosis Risk in Communities (ARIC) Study.
Methods
We generated a Gstm1 knockout mouse line to study its role in a CKD model (involving subtotal nephrectomy) and a hypertension model (induced by angiotensin II). We examined the effect of intake of cruciferous vegetables and GSTM1 genotypes on kidney disease in mice as well as in human ARIC study participants. We also examined the importance of superoxide in the mediating pathways and of hematopoietic GSTM1 on renal inflammation.
Results
Gstm1 knockout mice displayed increased oxidative stress, kidney injury, and inflammation in both models. The central mechanism for kidney injury is likely mediated by oxidative stress, because treatment with Tempol, an superoxide dismutase mimetic, rescued kidney injury in knockout mice without lowering BP. Bone marrow crosstransplantation revealed that Gstm1 deletion in the parenchyma, and not in bone marrow-derived cells, drives renal inflammation. Furthermore, supplementation with cruciferous broccoli powder rich in the precursor to antioxidant-activating sulforaphane significantly ameliorated kidney injury in Gstm1 knockout, but not wild-type mice. Similarly, among humans (ARIC study participants), high consumption of cruciferous vegetables was associated with fewer kidney failure events compared with low consumption, but this association was observed primarily in participants homozygous for the GSTM1 deletion variant.
Conclusions
Our data support a role for the GSTM1 enzyme in the modulation of oxidative stress, inflammation, and protective metabolites in CKD.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.
Confianza de la comunidad
Cargando…
¿Cuánto confías en los hallazgos de este estudio?
Comentarios
¿Algo está mal aquí?
Señala este estudio si su información, etiquetas o financiación parecen incorrectas. Un editor revisa cada señalamiento.
Información educativa sobre investigación publicada. No es consejo médico ni una recomendación para empezar o dejar nada.