Abstract P238: High Glucose Induces Interleukin-1β Synthesis In Renal Tubular Cells By Suppressing Autophagy
| Autor: | Jorge F Giani, Luciana C Veiras, Ellen Bernstein, Duoyao Cao, Zakir Khan, Kenneth E Bernstein |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Hypertension. 79 |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hyp.79.suppl_1.p238 |
| Popis: | We showed that IL-1β derived from renal tubular epithelial cells initiates the inflammatory response that promotes salt sensitivity during diabetes. Yet, the intracellular mechanism that mediates IL-1β synthesis by tubular cells is unknown. We hypothesize that high glucose inhibits autophagy in tubular cells resulting in the accumulation of mitochondrial reactive oxygen spices (mtROS) that activate the NLRP3 inflammasome to produce IL-1β. Thirty-week-old db/db mice, a model of type 2 diabetes, and db/+ non-diabetic controls (n=6) were exposed to high salt diet (4% NaCl) for 4 weeks. At the end, mean arterial pressure was higher in db/db vs. db/+ mice (125±7 vs. 104±4 mmHg, P+ E-cadherin + cells, P0.001) and displayed increased caspase-1 and NLRP3 expression compared to TECs exposed to low glucose (5mM). Autophagy analysis revealed low LCB3-II and high p62 suggesting that high glucose suppressed autophagy in tubular cells. This was associated with mtROS accumulation (1.9±0.2-fold increase, P |
| Databáze: | OpenAIRE |
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