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Collecting duct PGE2 responses reduce water loss with empagliflozin in mice with type 2 diabetes mellitus

Published on: 8th April, 2021

OCLC Number/Unique Identifier: 9022394723

Introduction: Sodium-glucose cotransporter 2 inhibitors such as empagliflozin (EMPA) protect against diabetic kidney disease. Prostaglandin E2 (PGE2) the main renal product of cyclooxygenase-2, inhibits vasopressin (AVP)-water reabsorption in the collecting duct (CD). The novelty of this study is that for the first time, we examined if EMPA affects the renal PGE2/EP receptor system and determined if CD responses to EMPA prevent water loss. Methods: Four groups of adult male mice were studied after 6 weeks of treatment: control (db/m), db/m+EMPA (10 mg/kg/day in chow), type 2 diabetic diabetic/dyslipidemia (db/db), and db/db+EMPA. Tubules were microdissected for quantitative polymerase chain reaction (qPCR) and CD water transport was measured in response to AVP, with or without PGE2. Results: Hyperglycemia and albuminuria were attenuated by EMPA. Renal mRNA expression for COX, PGE synthase, PGE2 (EP) receptor subtypes, CD AVP V2 receptors and aquaporin-2 was elevated in db/db mice, but unchanged by EMPA. Urine PGE2 levels increased in db/db but were unchanged by EMPA. AVP-water reabsorption was comparable in db/m and db/m+EMPA, and equally attenuated to 50% by PGE2. In db/db mice, AVP-water reabsorption was reduced by 50% compared to non-diabetic mice, and this reduction was unaffected by EMPA. In db/db mice, AVP-stimulated water transport was more significantly attenuated with PGE2 (62%), compared to non-diabetic mice, but this attenuation was reduced in response to EMPA, to 28%. Conclusion: In summary, expression of renal PGE2/EP receptors is increased in db/db mice, and this expression is unaffected by EMPA. However, in diabetic CD, PGE2 caused a greater attenuation in AVP-stimulated water reabsorption, and this attenuation is reduced by EMPA. This suggests that EMPA attenuates diabetes-induced excess CD water loss.
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A novel case of an infantile fibrosarcoma-like tumor with KIAA1549-BRAF translocation and an oncogenic NF2p.Q459* SNV with potential clinical significance

Published on: 27th August, 2021

OCLC Number/Unique Identifier: 9272372468

We report a case of a right gluteal mass from the sacroiliac joint to the knee of an infant girl. Biopsy showed histopathological features similar to infantile fibrosarcoma (IFS). However, unlike most IFS, no ETV6-NTRK3 fusion gene abnormality was detected. Molecular analysis with TruSight RNA Pan-Cancer Panel detected the presence of KIAA1549-BRAF translocation and an oncogenic NF2p.Q459* SNV with potential clinical significance. A review revealed that the combination of this patient’s tumor site with the presence of a KIAA1549-BRAF translocation abnormality and an accompanying single nucleotide variant has not been previously described. The detection of this translocation abnormality raises the possibility that the spindle cell tumors in infants with an absence of the ETV6-NTRK3 fusion gene abnormality might have a distinct pathogenetic mechanism different from the previously known IFS and congenital mesoblastic nephroma. Furthermore, the discovery of BRAF translocation and its aberrant signaling of the mitogen-activated protein kinase (MAPK) pathway in this tumor contributes to the promise of clinical benefit of using the MEKi trametinib for the treatment of progressive disease that is refractory to conventional chemotherapy. 
Cite this ArticleCrossMarkPublonsHarvard Library HOLLISGrowKudosResearchGateBase SearchOAI PMHAcademic MicrosoftScilitSemantic ScholarUniversite de ParisUW LibrariesSJSU King LibrarySJSU King LibraryNUS LibraryMcGillDET KGL BIBLiOTEKJCU DiscoveryUniversidad De LimaWorldCatVU on WorldCat
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