Glucose Induces IL-1α-Dependent Inflammation and Extracellular Matrix Proteins Expression and Deposition in Renal Tubular Epithelial Cells in Diabetic Kidney Disease
| العنوان: | Glucose Induces IL-1α-Dependent Inflammation and Extracellular Matrix Proteins Expression and Deposition in Renal Tubular Epithelial Cells in Diabetic Kidney Disease |
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| المؤلفون: | Talal Salti, Khaled Khazim, Rami Haddad, Salvatore Campisi-Pinto, Gil Bar-Sela, Idan Cohen |
| المصدر: | Frontiers in Immunology, Vol 11 (2020) Frontiers in Immunology |
| بيانات النشر: | Frontiers Media S.A., 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Fluorescent Antibody Technique, Extracellular matrix, Diabetic nephropathy, 0302 clinical medicine, Interleukin-1alpha, Immunology and Allergy, Diabetic Nephropathies, Kidney, Extracellular Matrix Proteins, biology, Chemistry, alarmins, Interleukin, Inflammasome, Calpain, Brief Research Report, Middle Aged, Immunohistochemistry, Cell biology, medicine.anatomical_structure, Kidney Tubules, Female, medicine.symptom, medicine.drug, Adult, lcsh:Immunologic diseases. Allergy, kidney, extracellular matrix, Immunology, Inflammation, interleukin 1, 03 medical and health sciences, Cell Line, Tumor, medicine, Humans, stressorin, diabetic nephropathy (DN), Aged, Epithelial Cells, medicine.disease, 030104 developmental biology, Glucose, Gene Expression Regulation, inflammation, biology.protein, lcsh:RC581-607, Biomarkers, 030215 immunology, Kidney disease |
| الوصف: | Diabetes mellitus is linked with metabolic stress that induces cellular damage and can provoke renal inflammation and fibrotic responses that eventually lead to chronic kidney disease. Because the inflammasome, interleukin 1 (IL-1), IL-1α/IL-β, and IL-1R are central elements of kidney inflammation and pharmacological IL-1R antagonist (IL-1Ra) was shown to prevent or even reverse diabetic nephropathy (DN) in animal models, we explored the intrinsic expression of IL-1 molecules in kidney tissue of DN patients as regulators of renal inflammation. We used biopsies taken from DN patients and controls and show a high level of IL-1α expression in renal tubular epithelial cells, whereas both IL-1 agonistic molecules (i.e., IL-1α and IL-1β) were devoid of the glomeruli. Human proximal tubular kidney HK-2 cells exposed to high glucose (HG) gradually increase the expression of IL-1α but not IL-1β and induce the expression and deposition of extracellular matrix (ECM) proteins. We further demonstrate that in vitro ectopic addition of recombinant IL-1α in low glucose concentration leads to a similar effect as in HG, while supplementing excess amounts of IL-1Ra in HG significantly attenuates the ECM protein overexpression and deposition. Accordingly, inhibition of IL-1α cleaving protease calpain, but not caspapse-1, also strongly reduces ECM protein production by HK-2 cells. Collectively, we demonstrate that IL-1α and not IL-1β, released from renal tubular cells is the key inflammatory molecule responsible for the renal inflammation in DN. Our result suggests that the clinical use of IL-1Ra in DN should be promoted over the individual neutralization of IL-1α or IL-1β in order to achieve better blocking of IL-1R signaling. |
| اللغة: | English |
| تدمد: | 1664-3224 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3694a82718575be39e38e16cc2bfce43Test https://www.frontiersin.org/article/10.3389/fimmu.2020.01270/fullTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3694a82718575be39e38e16cc2bfce43 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16643224 |
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