ArticleThe Journal of biological chemistry
Cardio- and reno-protective effects of dipeptidyl peptidase III in diabetic mice.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- Novel aspects of the renin-angiotensin-aldosterone system in septic shock.Current opinion in physiology · 2026Article
- The Role of the C3a-C3aR Pathway in Diseases: Latest Research Advances.Mediators of inflammation · 2026Review
- Reimagining risk stratification: Dipeptidyl peptidase 3 in the new era of cardiovascular biomarkers.World journal of cardiology · 2025Article
- One Enzyme, Many Faces: The Expanding Role of DPP3 in Cardiovascular and Critical Care.Journal of clinical medicine · 2025Review
- Shared signaling pathways and comprehensive therapeutic approaches among diabetes complications.Frontiers in medicine · 2024Review
- Pathomechanisms of Diabetic Kidney Disease.Journal of clinical medicine · 2023Review
- Identification of an Additional Metal-Binding Site in Human Dipeptidyl Peptidase III.International journal of molecular sciences · 2023Article
- Diabetic vascular diseases: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2023Review
- Emerging Therapy for Diabetic Cardiomyopathy: From Molecular Mechanism to Clinical Practice.Biomedicines · 2023Review
- Structural and Functional Characterization of a New Bacterial Dipeptidyl Peptidase III Involved in Fruiting Body Formation in Myxobacteria.International journal of molecular sciences · 2022Article
- Activation of complement C1q and C3 in glomeruli might accelerate the progression of diabetic nephropathy: Evidence from transcriptomic data and renal histopathology.Journal of diabetes investigation · 2022Article
- Identification of the Potential Molecular Mechanism ofComputational and mathematical methods in medicine · 2022Article
- DPP3: From biomarker to therapeutic target of cardiovascular diseases.Frontiers in cardiovascular medicine · 2022Review
- The role of protein kinase C in diabetic microvascular complications.Frontiers in endocrinology · 2022Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetes mellitus (DM) causes injury to tissues and organs, including to the heart and kidney, resulting in increased morbidity and mortality. Thus, novel potential therapeutics are continuously required to minimize DM-related organ damage. We have previously shown that dipeptidyl peptidase III (DPPIII) has beneficial roles in a hypertensive mouse model, but it is unknown whether DPPIII has any effects on DM. In this study, we found that intravenous administration of recombinant DPPIII in diabetic db/db mice for 8 weeks suppressed the DM-induced cardiac diastolic dysfunctions and renal injury without alteration of the blood glucose level. This treatment inhibited inflammatory cell infiltration and fibrosis in the heart and blocked the increase in albuminuria by attenuating the disruption of the glomerular microvasculature and inhibiting the effacement of podocyte foot processes in the kidney. The beneficial role of DPPIII was, at least in part, mediated by the cleavage of a cytotoxic peptide, named Peptide 2, which was increased in db/db mice compared with normal mice. This peptide consisted of nine amino acids, was a digested fragment of complement component 3 (C3), and had an anaphylatoxin-like effect determined by the Miles assay and chemoattractant analysis. The effect was dependent on its interaction with the C3a receptor and protein kinase C-mediated RhoA activation downstream of the receptor in endothelial cells. In conclusion, DPPIII plays a protective role in the heart and kidney in a DM animal model through cleavage of a peptide that is a part of C3.
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