ArticleBioscience reports2019
Pioglitazone protects blood vessels through inhibition of the apelin signaling pathway by promoting KLF4 expression in rat models of T2DM.
Article in Bioscience reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 9 citations in OpenAlex.
- Context‑dependent duality of the apelin/elabela‑APJ system in diabetes and its complications (Review).International journal of molecular medicine · 2026Review
- Apelin/APJ alleviates diabetic nephropathy by improving glomerular endothelial cells dysfunction via SIRT3‑KLF15.Molecular medicine reports · 2025Article
- The Role of Apelin-APJ System in Diabetes and Obesity.Frontiers in endocrinology · 2022Review
- Elevated circulating Krüppel-like factor 4 level as a novel independent marker of the proatherogenic risk in patients with psoriasis: a preliminary study.Postepy dermatologii i alergologii · 2021Article
- Exogenous Hydrogen Sulfide Ameliorates Diabetic Myocardial Fibrosis by Inhibiting Cell Aging Through SIRT6/AMPK Autophagy.Frontiers in pharmacology · 2020Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
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Abstract
Apelin, identified as the endogenous ligand of APJ, exerts various cardiovascular effects. However, the molecular mechanism underlying the regulation of apelin expression in vascular cells is poorly described. Pioglitazone (PIO) and Krüppel-like factor 4 (KLF4) exhibit specific biological functions on vascular physiology and pathophysiology by regulating differentiation- and proliferation-related genes. The present study aimed to investigate the roles of PIO and KLF4 in the transcriptional regulation of apelin in a high-fat diet/streptozotocin rat model of diabetes and in PIO-stimulated vascular smooth muscle cells (VSMCs). Immunohistochemistry, qRT-PCR, and Western blotting assays revealed that the aorta of the Type 2 diabetes mellitus (T2DM) rat models had a high expression of apelin, PIO could decrease the expression of apelin in the PIO-treated rats. In vitro, Western blotting assays and immunofluorescent staining results showed that the basal expression of apelin was decreased but that of KLF4 was increased when VSMCs were stimulated by PIO treatment. Luciferase and chromatin immunoprecipitation assay results suggested that KLF4 bound to the GKLF-binding site of the apelin promoter and negatively regulated the transcription activity of apelin in VSMCs under PIO stimulation. Furthermore, qRT-PCR and Western blotting assay results showed that the overexpression of KLF4 markedly decreased the basal expression of apelin, but the knockdown of KLF4 restored the PIO-induced expression of apelin. In conclusion, PIO inhibited the expression of apelin in T2DM rat models to prevent diabetic macroangiopathy, and negatively regulated the gene transcription of apelin by promoting transcription of KLF4 in the apelin promoter.
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