395 Systemic Administration of miR-451 Improves Autophagy Response in an Accelerated Mouse Model of Diabetic Kidney Disease
OBJECTIVES/GOALS: Diabetic Kidney Disease (DKD) is a common diabetes complication, often linked to end-stage renal disease in the United States (US). While autophagy and miRNAs are pivotal, miR-451’s specific role remains understudied. Our study explores its renoprotective effects in an accelerated...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Cambridge University Press
2024-04-01
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| Series: | Journal of Clinical and Translational Science |
| Online Access: | https://www.cambridge.org/core/product/identifier/S2059866124003455/type/journal_article |
| _version_ | 1797226931487244288 |
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| author | Sadaf Ghaderzadeh Baiyeendang Agbor-Baiyee Chidera Obiwuma Neal Mohit Kanwal K. Gambhir Carolyn M. Ecelbarger Maurice B. Fluitt |
| author_facet | Sadaf Ghaderzadeh Baiyeendang Agbor-Baiyee Chidera Obiwuma Neal Mohit Kanwal K. Gambhir Carolyn M. Ecelbarger Maurice B. Fluitt |
| author_sort | Sadaf Ghaderzadeh |
| collection | DOAJ |
| description | OBJECTIVES/GOALS: Diabetic Kidney Disease (DKD) is a common diabetes complication, often linked to end-stage renal disease in the United States (US). While autophagy and miRNAs are pivotal, miR-451’s specific role remains understudied. Our study explores its renoprotective effects in an accelerated DKD mouse model. METHODS/STUDY POPULATION: We assessed the effect of miR-451 mimic treatment on Diabetic Kidney Disease (DKD) in BTBR ob/ob mice, known for their rapid DKD-like renal lesions. Mice were divided into four groups: WT (wild-type), BTBR ob/ob, WT+miR-451 (wild-type with miR-451 mimic), and BTBR ob/ob+miR-451 (BTBR ob/ob with miR-451 mimic). MiR-451 mimics were administered at 2mg/kg body weight once weekly for three consecutive weeks. We collected spot urine and monitored blood glucose levels at each time point. After the treatment period, mice were euthanized for kidney and blood samples. Western blot analysis assessed autophagy-related protein markers. Statistical analysis included Student’s t-test and ANOVA (p<0.05). RESULTS/ANTICIPATED RESULTS: The study assessed the impact of miR-451 mimic treatment in BTBR ob/ob mice. Albumin:creatinine ratio increased fourfold (p=0.01) in BTBR ob/ob mice at 5 weeks. MiR-451 mimic treatment had no impact on body weight. Blood glucose levels were notably higher in both treated and untreated BTBR ob/ob mice at 12 (425±33.1 mg/dL; p=0.04) and 13 weeks (383±25.3 mg/dL; p=0.007). However, a significant drop occurred from week 13 (554.7±10.8 mg/dL) to week 14 (289±13.3 mg/dL; p=0.0002) in BTBR ob/ob miR-451 treated mice. Western blot analysis in whole kidney homogenates showed a 91% reduction (p=0.02) in YWHAZ, a predicted miR-451 target, in treated BTBR ob/ob mice and a 95% reduction (p=0.01) in WT mice. Furthermore, miR-451 mimic treatment led to a 68% increase (p=0.01) in ATG101 and a 44% increase in Beclin-1 in BTBR ob/ob mice. DISCUSSION/SIGNIFICANCE: The study uncovers miR-451-based interventions as a promising avenue to counter Diabetic Kidney Disease by modulating autophagy, potentially introducing novel therapies for at-risk individuals. However, practical DKD treatments will require further research and rigorous clinical validation to harness the full potential of these insights. |
| first_indexed | 2024-04-24T14:32:45Z |
| format | Article |
| id | doaj.art-aff846a53b054fa69ffce73d31a11d9d |
| institution | Directory Open Access Journal |
| issn | 2059-8661 |
| language | English |
| last_indexed | 2024-04-24T14:32:45Z |
| publishDate | 2024-04-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | Journal of Clinical and Translational Science |
| spelling | doaj.art-aff846a53b054fa69ffce73d31a11d9d2024-04-03T02:00:06ZengCambridge University PressJournal of Clinical and Translational Science2059-86612024-04-01811811810.1017/cts.2024.345395 Systemic Administration of miR-451 Improves Autophagy Response in an Accelerated Mouse Model of Diabetic Kidney DiseaseSadaf Ghaderzadeh0Baiyeendang Agbor-Baiyee1Chidera Obiwuma2Neal Mohit3Kanwal K. Gambhir4Carolyn M. Ecelbarger5Maurice B. Fluitt6Division of Endocrinology and Metabolism, Deparmtent of Medicine, Howard University College of MedicineDivision of Endocrinology and Metabolism, Deparmtent of Medicine, Howard University College of MedicineDivision of Endocrinology and Metabolism, Deparmtent of Medicine, Howard University College of MedicineDivision of Endocrinology and Metabolism, Deparmtent of Medicine, Howard University College of MedicineDivision of Endocrinology and Metabolism, Deparmtent of Medicine, Howard University College of MedicineDivision of Endocrinology and Metabolism, Department of Medicine, Georgetown UniversityDivision of Endocrinology and Metabolism, Deparmtent of Medicine, Howard University College of MedicineOBJECTIVES/GOALS: Diabetic Kidney Disease (DKD) is a common diabetes complication, often linked to end-stage renal disease in the United States (US). While autophagy and miRNAs are pivotal, miR-451’s specific role remains understudied. Our study explores its renoprotective effects in an accelerated DKD mouse model. METHODS/STUDY POPULATION: We assessed the effect of miR-451 mimic treatment on Diabetic Kidney Disease (DKD) in BTBR ob/ob mice, known for their rapid DKD-like renal lesions. Mice were divided into four groups: WT (wild-type), BTBR ob/ob, WT+miR-451 (wild-type with miR-451 mimic), and BTBR ob/ob+miR-451 (BTBR ob/ob with miR-451 mimic). MiR-451 mimics were administered at 2mg/kg body weight once weekly for three consecutive weeks. We collected spot urine and monitored blood glucose levels at each time point. After the treatment period, mice were euthanized for kidney and blood samples. Western blot analysis assessed autophagy-related protein markers. Statistical analysis included Student’s t-test and ANOVA (p<0.05). RESULTS/ANTICIPATED RESULTS: The study assessed the impact of miR-451 mimic treatment in BTBR ob/ob mice. Albumin:creatinine ratio increased fourfold (p=0.01) in BTBR ob/ob mice at 5 weeks. MiR-451 mimic treatment had no impact on body weight. Blood glucose levels were notably higher in both treated and untreated BTBR ob/ob mice at 12 (425±33.1 mg/dL; p=0.04) and 13 weeks (383±25.3 mg/dL; p=0.007). However, a significant drop occurred from week 13 (554.7±10.8 mg/dL) to week 14 (289±13.3 mg/dL; p=0.0002) in BTBR ob/ob miR-451 treated mice. Western blot analysis in whole kidney homogenates showed a 91% reduction (p=0.02) in YWHAZ, a predicted miR-451 target, in treated BTBR ob/ob mice and a 95% reduction (p=0.01) in WT mice. Furthermore, miR-451 mimic treatment led to a 68% increase (p=0.01) in ATG101 and a 44% increase in Beclin-1 in BTBR ob/ob mice. DISCUSSION/SIGNIFICANCE: The study uncovers miR-451-based interventions as a promising avenue to counter Diabetic Kidney Disease by modulating autophagy, potentially introducing novel therapies for at-risk individuals. However, practical DKD treatments will require further research and rigorous clinical validation to harness the full potential of these insights.https://www.cambridge.org/core/product/identifier/S2059866124003455/type/journal_article |
| spellingShingle | Sadaf Ghaderzadeh Baiyeendang Agbor-Baiyee Chidera Obiwuma Neal Mohit Kanwal K. Gambhir Carolyn M. Ecelbarger Maurice B. Fluitt 395 Systemic Administration of miR-451 Improves Autophagy Response in an Accelerated Mouse Model of Diabetic Kidney Disease Journal of Clinical and Translational Science |
| title | 395 Systemic Administration of miR-451 Improves Autophagy Response in an Accelerated Mouse Model of Diabetic Kidney Disease |
| title_full | 395 Systemic Administration of miR-451 Improves Autophagy Response in an Accelerated Mouse Model of Diabetic Kidney Disease |
| title_fullStr | 395 Systemic Administration of miR-451 Improves Autophagy Response in an Accelerated Mouse Model of Diabetic Kidney Disease |
| title_full_unstemmed | 395 Systemic Administration of miR-451 Improves Autophagy Response in an Accelerated Mouse Model of Diabetic Kidney Disease |
| title_short | 395 Systemic Administration of miR-451 Improves Autophagy Response in an Accelerated Mouse Model of Diabetic Kidney Disease |
| title_sort | 395 systemic administration of mir 451 improves autophagy response in an accelerated mouse model of diabetic kidney disease |
| url | https://www.cambridge.org/core/product/identifier/S2059866124003455/type/journal_article |
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