FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2903790666> ?p ?o ?g. }

• W2903790666 abstract "Angiotensin-converting enzyme (ACE) plays a key role in renal inflammation and sodium retention associated with diabetic nephropathy. Although most effects of ACE have been classically related to angiotensin (Ang) II synthesis, studies highlight an Ang II-independent role of ACE in inflammation. Indeed, ACE has two catalytic domains, the N- and C-domains, that can process a wide diversity of substrates besides Ang I. Here, we study the relative contributions of ACE domains to renal inflammation and sodium retention during diabetic nephropathy. Diabetes was induced with streptozotocin in wild-type (WT) mice and mice lacking either a functional ACE N-domain (NKO) or C-domain (CKO) (n=5-8). After 6 months of diabetes, we evaluated the natriuretic response to volume expansion. For this, mice were injected with 0.9% NaCl equivalent to 10% of their body weight. After 5 hours, diabetic NKO mice excreted 30% more urinary sodium in response to the saline challenge compared to diabetic WT or CKO mice ( P <0.05). This enhanced natriuretic response was associated with a 47% reduction ( P <0.05) of renal epithelial sodium channel (ENaC) cleaved (active) α and γ subunits. Further, diabetic NKO displayed lower levels of renal fibrosis (46% reduction, P <0.05), IL-1β (56% reduction, P <0.05), TNFα (50% reduction, P <0.05) and albuminuria (53% reduction, P <0.01) compared to WT and CKO diabetic mice. This protective phenotype was not associated with changes in renal Ang II levels (WT: 237 ± 73; NKO: 283 ± 53 CKO: 245 ± 39 fmol/g kidney, P =NS). We next evaluated whether the anti-inflammatory tetrapeptide N-acetyl-seryl-asparyl-lysyl-proline (AcSDKP), an ACE N-domain specific substrate, mediates the protective phenotype of NKO. For this, diabetic mice were treated with the prolyl oligopeptidase inhibitor, S17092 (10 mg/kg, IP), that prevents the synthesis of AcSDKP. In diabetic NKO mice receiving S17092, sodium excretion in response to a saline challenge, ENaC α and γ subunit cleavage, renal inflammation and renal injury were indistinguishable from equally treated diabetic WT mice. In summary, these data indicate that increasing AcSDKP by blocking the ACE N-domain improves sodium handling and ameliorates diabetic kidney disease independently of intrarenal Ang II regulation." @default.
• W2903790666 created "2018-12-22" @default.
• W2903790666 creator A5002212151 @default.
• W2903790666 creator A5003134867 @default.
• W2903790666 creator A5008800075 @default.
• W2903790666 creator A5012879895 @default.
• W2903790666 creator A5016174385 @default.
• W2903790666 creator A5020244444 @default.
• W2903790666 creator A5047889109 @default.
• W2903790666 creator A5055775850 @default.
• W2903790666 creator A5066229372 @default.
• W2903790666 creator A5069267783 @default.
• W2903790666 creator A5089199440 @default.
• W2903790666 date "2018-09-01" @default.
• W2903790666 modified "2023-10-18" @default.
• W2903790666 title "Abstract 035: Increasing Renal AcSDKP by Eliminating the ACE N-Domain Blocks Renal Inflammation and Sodium Retention During Diabetic Nephropathy" @default.
• W2903790666 doi "https://doi.org/10.1161/hyp.72.suppl_1.035" @default.
• W2903790666 hasPublicationYear "2018" @default.
• W2903790666 type Work @default.
• W2903790666 sameAs 2903790666 @default.
• W2903790666 citedByCount "0" @default.
• W2903790666 crossrefType "journal-article" @default.
• W2903790666 hasAuthorship W2903790666A5002212151 @default.
• W2903790666 hasAuthorship W2903790666A5003134867 @default.
• W2903790666 hasAuthorship W2903790666A5008800075 @default.
• W2903790666 hasAuthorship W2903790666A5012879895 @default.
• W2903790666 hasAuthorship W2903790666A5016174385 @default.
• W2903790666 hasAuthorship W2903790666A5020244444 @default.
• W2903790666 hasAuthorship W2903790666A5047889109 @default.
• W2903790666 hasAuthorship W2903790666A5055775850 @default.
• W2903790666 hasAuthorship W2903790666A5066229372 @default.
• W2903790666 hasAuthorship W2903790666A5069267783 @default.
• W2903790666 hasAuthorship W2903790666A5089199440 @default.
• W2903790666 hasConcept C126322002 @default.
• W2903790666 hasConcept C126894567 @default.
• W2903790666 hasConcept C134018914 @default.
• W2903790666 hasConcept C174459258 @default.
• W2903790666 hasConcept C178790620 @default.
• W2903790666 hasConcept C185592680 @default.
• W2903790666 hasConcept C2776174234 @default.
• W2903790666 hasConcept C2776914184 @default.
• W2903790666 hasConcept C2779922275 @default.
• W2903790666 hasConcept C2780091579 @default.
• W2903790666 hasConcept C2781184683 @default.
• W2903790666 hasConcept C537181965 @default.
• W2903790666 hasConcept C555293320 @default.
• W2903790666 hasConcept C71924100 @default.
• W2903790666 hasConceptScore W2903790666C126322002 @default.
• W2903790666 hasConceptScore W2903790666C126894567 @default.
• W2903790666 hasConceptScore W2903790666C134018914 @default.
• W2903790666 hasConceptScore W2903790666C174459258 @default.
• W2903790666 hasConceptScore W2903790666C178790620 @default.
• W2903790666 hasConceptScore W2903790666C185592680 @default.
• W2903790666 hasConceptScore W2903790666C2776174234 @default.
• W2903790666 hasConceptScore W2903790666C2776914184 @default.
• W2903790666 hasConceptScore W2903790666C2779922275 @default.
• W2903790666 hasConceptScore W2903790666C2780091579 @default.
• W2903790666 hasConceptScore W2903790666C2781184683 @default.
• W2903790666 hasConceptScore W2903790666C537181965 @default.
• W2903790666 hasConceptScore W2903790666C555293320 @default.
• W2903790666 hasConceptScore W2903790666C71924100 @default.
• W2903790666 hasIssue "Suppl_1" @default.
• W2903790666 hasLocation W29037906661 @default.
• W2903790666 hasOpenAccess W2903790666 @default.
• W2903790666 hasPrimaryLocation W29037906661 @default.
• W2903790666 hasRelatedWork W1980339709 @default.
• W2903790666 hasRelatedWork W2038657938 @default.
• W2903790666 hasRelatedWork W2061298156 @default.
• W2903790666 hasRelatedWork W2077747914 @default.
• W2903790666 hasRelatedWork W2077791200 @default.
• W2903790666 hasRelatedWork W2106269091 @default.
• W2903790666 hasRelatedWork W2127085070 @default.
• W2903790666 hasRelatedWork W2367890389 @default.
• W2903790666 hasRelatedWork W2402585689 @default.
• W2903790666 hasRelatedWork W4233814061 @default.
• W2903790666 hasVolume "72" @default.
• W2903790666 isParatext "false" @default.
• W2903790666 isRetracted "false" @default.
• W2903790666 magId "2903790666" @default.
• W2903790666 workType "article" @default.