ArticleCell & bioscience2024
Transcription and post-translational mechanisms: dual regulation of adiponectin-mediated Occludin expression in diabetes.
Article in Cell & bioscience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Vascular Endothelial Barrier in Salivary Glands: From Physiological Regulation to Pathological Impairment of Secretion.International journal of molecular sciences · 2026Review
- Targeting post-translational modifications: novel insights into bone metabolic diseases.Journal of advanced research · 2026Review
- Occludin-mediated barrier dysfunction and its role in cardiovascular and cerebrovascular pathogenesis.Frontiers in cardiovascular medicine · 2026Review
- Music of Different Tones Maintains Intestinal Immunity by Regulating the Intestinal Barrier and Intestinal Microbiota.International journal of molecular sciences · 2025Article
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11 authors.
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Abstract
backgroundOccludin, a crucial component of tight junctions, has emerged as a promising biomarker for the diagnosis of acute ischemic disease, highlighting its significant potential in clinical applications. In the diabetes, Occludin serves as a downstream target gene intricately regulated by the adiponectin (APN) signaling pathway. However, the specific mechanism by which adiponectin regulates Occludin expression remains unclear. METHODS AND
resultsEndothelial-specific Ocln knockdown reduced APN-mediated blood flow recovery after femoral artery ligation and nullified APN's protection against high-fat diet (HFD)-triggered apoptosis and angiogenesis inhibition in vivo. Mechanically, we have meticulously elucidated APN's regulatory role in Occludin expression through a comprehensive analysis spanning transcriptional and post-translational dimensions. Foxo1 has been elucidated as a crucial transcriptional regulator of Occludin that is modulated by the APN/APPL1 signaling axis, as evidenced by validation through ChIP-qPCR assays and Western blot analysis. APN hindered Occludin degradation via the ubiquitin-proteasome pathway. Mass spectrometry analysis has recently uncovered a novel phosphorylation site, Tyr467, on Occludin. This site responds to APN, playing a crucial role in inhibiting Occludin ubiquitination by APN. The anti-apoptotic and pro-angiogenic effects of APN were attenuated in vitro and in vivo following Foxo1 knockdown or expression of a non-phosphorylatable mutant, OccludinY467A. Clinically, elevated plasma concentrations of Occludin were observed in patients with diabetes. A significant negative correlation was found between Occludin levels and APN concentrations.
conclusionOur study proposes that APN modulates Occludin expression through mechanisms involving both transcriptional and post-translational interactions, thereby conferring a protective effect on endothelial integrity within diabetic vasculature.
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