Endothelial Cell-Specific Molecule-1 ...
Document type :
Article dans une revue scientifique: Article original
DOI :
Title :
Endothelial Cell-Specific Molecule-1 Inhibits Albuminuria in Diabetic Mice
Author(s) :
Zheng, Xiaoyi [Auteur]
Higdon, Lauren [Auteur]
Gaudet, Alexandre [Auteur]
Shah, Manav [Auteur]
Balistieri, Angela [Auteur]
Li, Catherine [Auteur]
Nadai, Patricia [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Palaniappan, Latha [Auteur]
Yang, Xiaoping [Auteur]
Santo, Briana [Auteur]
Ginley, Brandon [Auteur]
Wang, Xiaoxin [Auteur]
Myakala, Komuraiah [Auteur]
Nallagatla, Pratima [Auteur]
Levi, Moshe [Auteur]
Sarder, Pinaki [Auteur]
Rosenberg, Avi [Auteur]
Maltzman, Jonathan [Auteur]
de Freitas Caires, Nathalie [Auteur]
Bhalla, Vivek [Auteur]
Higdon, Lauren [Auteur]
Gaudet, Alexandre [Auteur]
Shah, Manav [Auteur]
Balistieri, Angela [Auteur]
Li, Catherine [Auteur]
Nadai, Patricia [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Palaniappan, Latha [Auteur]
Yang, Xiaoping [Auteur]
Santo, Briana [Auteur]
Ginley, Brandon [Auteur]
Wang, Xiaoxin [Auteur]
Myakala, Komuraiah [Auteur]
Nallagatla, Pratima [Auteur]
Levi, Moshe [Auteur]
Sarder, Pinaki [Auteur]
Rosenberg, Avi [Auteur]
Maltzman, Jonathan [Auteur]
de Freitas Caires, Nathalie [Auteur]
Bhalla, Vivek [Auteur]
Journal title :
Kidney360
Pages :
2059-2076
Publisher :
Wolters Kluwer Health Inc. on behalf of the American Society of Nephrology
Publication date :
2021-10-15
ISSN :
2641-7650
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Abstract Diabetic kidney disease (DKD) is the most common cause of kidney failure in the world, and novel predictive biomarkers and molecular mechanisms of disease are needed. Endothelial cell-specific molecule-1 (Esm-1) ...
Show more >Abstract Diabetic kidney disease (DKD) is the most common cause of kidney failure in the world, and novel predictive biomarkers and molecular mechanisms of disease are needed. Endothelial cell-specific molecule-1 (Esm-1) is a secreted proteoglycan that attenuates inflammation. We previously identified that a glomerular deficiency of Esm-1 associates with more pronounced albuminuria and glomerular inflammation in DKD-susceptible relative to DKD-resistant mice, but its contribution to DKD remains unexplored. In this study, we show that lower circulating Esm-1 predicts progressive stages of albuminuria in patients with diabetes. In DKD-susceptible mice, Esm-1 inversely correlates with albuminuria and glomerular leukocyte infiltration. Using hydrodynamic tail-vein injection, we show that over-expression of either mouse or human Esm-1 reduces diabetes-induced albuminuria relative to saline-injected controls independent of leukocyte infiltration. Using a complementary approach, we find that constitutive deletion of Esm-1 in DKD-resistant mice increases the degree of diabetes-induced albuminuria versus wild-type controls. Mechanistically, over-expression of Esm-1 attenuates diabetes-induced podocyte injury. By glomerular RNAseq, we identify that Esm-1 attenuates diabetes-induced up-regulation of interferon-stimulated genes, and Esm-1 inhibits expression of kidney disease-promoting and interferon-related genes, including Ackr2 and Cxcl11 . In conclusion, we demonstrate that Esm-1 protects against diabetes-induced albuminuria, and podocytopathy, possibly through select interferon signaling.Show less >
Show more >Abstract Diabetic kidney disease (DKD) is the most common cause of kidney failure in the world, and novel predictive biomarkers and molecular mechanisms of disease are needed. Endothelial cell-specific molecule-1 (Esm-1) is a secreted proteoglycan that attenuates inflammation. We previously identified that a glomerular deficiency of Esm-1 associates with more pronounced albuminuria and glomerular inflammation in DKD-susceptible relative to DKD-resistant mice, but its contribution to DKD remains unexplored. In this study, we show that lower circulating Esm-1 predicts progressive stages of albuminuria in patients with diabetes. In DKD-susceptible mice, Esm-1 inversely correlates with albuminuria and glomerular leukocyte infiltration. Using hydrodynamic tail-vein injection, we show that over-expression of either mouse or human Esm-1 reduces diabetes-induced albuminuria relative to saline-injected controls independent of leukocyte infiltration. Using a complementary approach, we find that constitutive deletion of Esm-1 in DKD-resistant mice increases the degree of diabetes-induced albuminuria versus wild-type controls. Mechanistically, over-expression of Esm-1 attenuates diabetes-induced podocyte injury. By glomerular RNAseq, we identify that Esm-1 attenuates diabetes-induced up-regulation of interferon-stimulated genes, and Esm-1 inhibits expression of kidney disease-promoting and interferon-related genes, including Ackr2 and Cxcl11 . In conclusion, we demonstrate that Esm-1 protects against diabetes-induced albuminuria, and podocytopathy, possibly through select interferon signaling.Show less >
Language :
Anglais
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
Source :
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