Small Extracellular Vesicles with a High Sphingomyelin Content Isolated from Hypertensive Diabetic db/db Mice Inhibits Calcium Mobilization and Augments Amiloride-Sensitive Epithelial Sodium Channel Activity Article Swipe
H Ramsay
,
Ling Yu
,
Faisal Alousi
,
Abdel A. Alli
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3390/biology14030252
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3390/biology14030252
Extracellular vesicles (EVs) contain bioactive lipids that play a key role in pathophysiology. We hypothesized that EVs released from salt-loaded hypertensive diabetic db/db mice have increased bioactive lipid content that inhibits intracellular calcium mobilization and increases the activity of renal epithelial sodium channels (ENaC). An enrichment of sphingomyelins (SMs) was found in small urinary EVs (uEVs) isolated from salt-loaded hypertensive diabetic db/db mice (n = 4) compared to non-salt loaded db/db mice with diabetes alone (n = 4). Both groups of mice were included in the same cohort to control for variability. Cultured mouse cortical collecting duct (mpkCCD) cells loaded with a calcium reporter dye and challenged with small uEVs from hypertensive diabetic db/db mice showed a decrease in calcium mobilization when compared to cells treated with small uEVs from diabetic db/db mice. The amiloride-sensitive transepithelial current was increased in mpkCCD cells treated with small uEVs with abundant sphingomyelin content from hypertensive diabetic db/db mice in a dose- and time-dependent manner. Similar results were observed in mpkCCD cells and Xenopus 2F3 cells treated with exogenous sphingomyelin in a time-dependent manner. Single-channel patch clamp studies showed a decrease in ENaC activity in cells transiently transfected with sphingomyelin synthase 1/2 specific siRNA compared to non-targeting siRNA. These data suggest EVs with high sphingomyelin content positively regulate renal ENaC activity in a mechanism involving an inhibition of calcium mobilization.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/biology14030252
- https://www.mdpi.com/2079-7737/14/3/252/pdf?version=1740820123
- OA Status
- gold
- Cited By
- 1
- References
- 34
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4408116601
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https://openalex.org/W4408116601Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.3390/biology14030252Digital Object Identifier
- Title
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Small Extracellular Vesicles with a High Sphingomyelin Content Isolated from Hypertensive Diabetic db/db Mice Inhibits Calcium Mobilization and Augments Amiloride-Sensitive Epithelial Sodium Channel ActivityWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-03-01Full publication date if available
- Authors
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H Ramsay, Ling Yu, Faisal Alousi, Abdel A. AlliList of authors in order
- Landing page
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https://doi.org/10.3390/biology14030252Publisher landing page
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https://www.mdpi.com/2079-7737/14/3/252/pdf?version=1740820123Direct link to full text PDF
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goldOpen access status per OpenAlex
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https://www.mdpi.com/2079-7737/14/3/252/pdf?version=1740820123Direct OA link when available
- Concepts
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Amiloride, Endocrinology, Internal medicine, Epithelial sodium channel, Biology, Sphingomyelin, Calcium, Renal cortex, Extracellular, Calcium in biology, Kidney, Sodium, Cell biology, Medicine, Chemistry, Cholesterol, Organic chemistryTop concepts (fields/topics) attached by OpenAlex
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1Total citation count in OpenAlex
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2025: 1Per-year citation counts (last 5 years)
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10Other works algorithmically related by OpenAlex
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