Epigenetic regulation of Nrf2-Mediated angiogenesis in diabetic foot ulcer progression: Role of histone deacetylases.

Autor: Harithpriya K; Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, TN, 603210, India., Jayasuriya R; Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, TN, 603210, India., Milan KL; Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, TN, 603210, India., Juttada U; Department of Molecular Genetics, M.V. Hospital for Diabetes & Prof. M. Viswanathan Diabetes Research Centre, Royapuram, Chennai, India., Kumpatla S; Department of Molecular Genetics, M.V. Hospital for Diabetes & Prof. M. Viswanathan Diabetes Research Centre, Royapuram, Chennai, India., Viswanathan V; Department of Molecular Genetics, M.V. Hospital for Diabetes & Prof. M. Viswanathan Diabetes Research Centre, Royapuram, Chennai, India. Electronic address: drvijay@mvdiabetes.com., Ramkumar KM; Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, TN, 603210, India. Electronic address: ramkumak@srmist.edu.in.
Jazyk: angličtina
Zdroj: Archives of biochemistry and biophysics [Arch Biochem Biophys] 2024 Oct; Vol. 760, pp. 110133. Date of Electronic Publication: 2024 Aug 22.
DOI: 10.1016/j.abb.2024.110133
Abstrakt: Nuclear factor E2-related factor 2 (Nrf2), a redox-sensitive transcription factor, regulates proangiogenic mediators, and antioxidant and detoxification enzymes. However, hitherto its regulation in the progression of DFU was poorly examined. The regulation of Nrf2 has been reported to be affected by various factors, including histone deacetylase (HDACs) and DNA methylation. The present study aimed to profile all classes of HDACs and correlate them with Nrf2 and angiogenic markers in the tissue biopsies of different grades of DFU patients (n = 20 in each grade). The gene expression profile of Nrf2 and its downstream targets, angiogenic markers, and all classes of HDACs were assessed using qPCR. Spearman's correlation was performed to analyze the correlation of HDACs with Nrf2 and its downstream targets along with angiogenic markers. We observed a progressive decrease in the gene expression of Nrf2 and angiogenic markers such as VEGF, HIF-1α, and SDF-1α and also an increase in the TSP-2 expression in different grades of DFU. In parallel, a significant downregulation of HDAC2/8 and SIRT1/2/4 has been observed in various grades of DFU subjects. On the other hand, HDAC1/3/4/11 and SIRT3/5/6/7 showed upregulation in different grades of DFU and the maximum increase was observed in Grade 3 patients. A significant negative correlation between Nrf2 and HDAC4, angiogenic markers, and HDAC4 suggested the pivotal role of the HDAC4-regulated Nrf2-mediated angiogenesis among DFU subjects. We have generated a first line of evidence on the epigenetic regulation of Nrf2 and its correlation with angiogenesis in the progression of diabetic foot ulcers.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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