دورية أكاديمية
Preventive effects of vasohibin-2-targeting peptide vaccine for diabetic nephropathy.
| العنوان: | Preventive effects of vasohibin-2-targeting peptide vaccine for diabetic nephropathy. |
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| المؤلفون: | Nakashima Y; Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan., Tanabe K; Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan., Mifune T; Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan., Nakadoi T; Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan., Hayashi H; Department of Health Development and Medicine, Osaka University Graduate School of Medicine, Osaka, Japan., Nakagami H; Department of Health Development and Medicine, Osaka University Graduate School of Medicine, Osaka, Japan., Sato Y; New Industry Creation Hatchery Center, Tohoku University, Sendai, Japan., Wada J; Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan. |
| المصدر: | American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2024 Jun 01; Vol. 326 (6), pp. F1054-F1065. Date of Electronic Publication: 2024 May 02. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901990 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1466 (Electronic) Linking ISSN: 15221466 NLM ISO Abbreviation: Am J Physiol Renal Physiol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Bethesda, Md. : American Physiological Society, c1997- |
| مواضيع طبية MeSH: | Diabetic Nephropathies*/prevention & control , Diabetic Nephropathies*/pathology , Diabetic Nephropathies*/immunology , Diabetes Mellitus, Experimental* , Vaccines, Subunit*/pharmacology , Vaccines, Subunit*/immunology, Animals ; Male ; Albuminuria/prevention & control ; Mice, Inbred C57BL ; Angiopoietin-2/metabolism ; Mice ; Kidney Glomerulus/pathology ; Kidney Glomerulus/metabolism ; Kidney Glomerulus/immunology ; Angiogenic Proteins/metabolism ; Protein Subunit Vaccines |
| مستخلص: | Diabetic nephropathy remains the leading cause of end-stage kidney disease in many countries, and additional therapeutic targets are needed to prevent its development and progression. Some angiogenic factors are involved in the pathogenesis of diabetic nephropathy. Vasohibin-2 (VASH2) is a novel proangiogenic factor, and our previous study showed that glomerular damage is inhibited in diabetic Vash2 homozygous knockout mice. Therefore, we established a VASH2-targeting peptide vaccine as a tool for anti-VASH2 therapy in diabetic nephropathy. In this study, the preventive effects of the VASH2-targeting peptide vaccine against glomerular injury were examined in a streptozotocin (STZ)-induced diabetic mouse model. The mice were subcutaneously injected with the vaccine at two doses 2 wk apart and then intraperitoneally injected with 50 mg/kg STZ for 5 consecutive days. Glomerular injury was evaluated 20 wk after the first vaccination. Treatment with the VASH2-targeting peptide vaccine successfully induced circulating anti-VASH2 antibody without inflammation in major organs. Although the vaccination did not affect blood glucose levels, it significantly prevented hyperglycemia-induced increases in urinary albumin excretion and glomerular volume. The vaccination did not affect increased VASH2 expression but significantly inhibited renal angiopoietin-2 (Angpt2) expression in the diabetic mice. Furthermore, it significantly prevented glomerular macrophage infiltration. The preventive effects of vaccination on glomerular injury were also confirmed in db / db mice. Taken together, the results of this study suggest that the VASH2-targeting peptide vaccine may prevent diabetic glomerular injury in mice by inhibiting Angpt2-mediated microinflammation. NEW & NOTEWORTHY This study demonstrated preventive effects of VASH2-targeting peptide vaccine therapy on albuminuria and glomerular microinflammation in STZ-induced diabetic mouse model by inhibiting renal Angpt2 expression. The vaccination was also effective in db / db mice. The results highlight the importance of VASH2 in the pathogenesis of early-stage diabetic nephropathy and the practicability of anti-VASH2 strategy as a vaccine therapy. |
| معلومات مُعتمدة: | JP21K08278 Japan Society for the Promotion of Science London (JSPS) |
| فهرسة مساهمة: | Keywords: albuminuria; diabetic nephropathy; macrophages; peptide vaccine; vasohibin-2 |
| المشرفين على المادة: | 0 (Vaccines, Subunit) 0 (Angiopoietin-2) 0 (Angiogenic Proteins) 0 (Protein Subunit Vaccines) |
| تواريخ الأحداث: | Date Created: 20240502 Date Completed: 20240530 Latest Revision: 20240530 |
| رمز التحديث: | 20240530 |
| DOI: | 10.1152/ajprenal.00341.2023 |
| PMID: | 38695075 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1522-1466 |
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| DOI: | 10.1152/ajprenal.00341.2023 |