circRNAs May Be Involved in Dysfunction of Neutrophils of Type 2 Diabetic Mice through Regulation of Specific miRNAs

Diabetes is known to delay wound healing, and this delay is attributed to prolonged inflammation. We found that microRNAs (miRNAs) might be involved in the dysfunction of diabetic-derived neutrophils, and dynamics of neutrophil and chronic inflammation might be initiated by miRNA-regulated genes. Mo...

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Main Authors: Takahiro Umehara, Ryoichi Mori, Kimberly A. Mace, Katsumi Tanaka, Noriho Sakamoto, Kazuya Ikematsu, Hiroaki Sato
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/10/12/3129
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author Takahiro Umehara
Ryoichi Mori
Kimberly A. Mace
Katsumi Tanaka
Noriho Sakamoto
Kazuya Ikematsu
Hiroaki Sato
author_facet Takahiro Umehara
Ryoichi Mori
Kimberly A. Mace
Katsumi Tanaka
Noriho Sakamoto
Kazuya Ikematsu
Hiroaki Sato
author_sort Takahiro Umehara
collection DOAJ
description Diabetes is known to delay wound healing, and this delay is attributed to prolonged inflammation. We found that microRNAs (miRNAs) might be involved in the dysfunction of diabetic-derived neutrophils, and dynamics of neutrophil and chronic inflammation might be initiated by miRNA-regulated genes. Moreover, studies of miRNA function in nephropathy have suggested that circular RNAs (circRNAs), which function as sponges of miRNA to regulate their expression, are potential biomarkers and new therapeutic targets for the diagnosis of diabetic nephropathy. Accordingly, to investigate the molecular mechanism of the regulation of inflammation in diabetic-derived neutrophils, we identified circRNAs in diabetic-derived neutrophils obtained from BKS.Cg-<i>Dock7<sup>m</sup> +/+ Lepr<sup>db</sup></i>/J (<i>Lepr<sup>db/db</sup></i> and <i>Lepr<sup>db/+</sup></i>) mice using microarrays. Neutrophils from pooled bone marrow of three diabetic and three non-diabetic mice were isolated and total RNA was extracted. Microarray analysis was performed using the Arraystar Mouse Circular RNA Array. The results showed that three circRNAs were significantly increased and six circRNAs were significantly decreased in diabetic-derived neutrophils compared with non-diabetic-derived neutrophils. The expressions of some circRNAs in diabetic-derived neutrophils were more than double those in non-diabetic-derived neutrophils. The circRNAs contain binding sites of miRNAs, which were differentially expressed in diabetic-derived neutrophils. Our results suggest that circRNAs may be involved in the regulation of inflammation in diabetic-derived neutrophils.
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spelling doaj.art-e12ed60c380a495aaebf9547645b5ed32023-11-24T13:27:20ZengMDPI AGBiomedicines2227-90592022-12-011012312910.3390/biomedicines10123129circRNAs May Be Involved in Dysfunction of Neutrophils of Type 2 Diabetic Mice through Regulation of Specific miRNAsTakahiro Umehara0Ryoichi Mori1Kimberly A. Mace2Katsumi Tanaka3Noriho Sakamoto4Kazuya Ikematsu5Hiroaki Sato6Department of Forensic Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka 807-8555, JapanDepartment of Pathology, Graduate School of Biomedical Sciences, School of Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, JapanDivision of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PT, UKDepartment of Plastic and Reconstructive Surgery, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, JapanDepartment of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, JapanDivision of Forensic Pathology and Science, Department of Medical and Dental Sciences, Graduate School of Biomedical Sciences, School of Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, JapanDepartment of Forensic Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka 807-8555, JapanDiabetes is known to delay wound healing, and this delay is attributed to prolonged inflammation. We found that microRNAs (miRNAs) might be involved in the dysfunction of diabetic-derived neutrophils, and dynamics of neutrophil and chronic inflammation might be initiated by miRNA-regulated genes. Moreover, studies of miRNA function in nephropathy have suggested that circular RNAs (circRNAs), which function as sponges of miRNA to regulate their expression, are potential biomarkers and new therapeutic targets for the diagnosis of diabetic nephropathy. Accordingly, to investigate the molecular mechanism of the regulation of inflammation in diabetic-derived neutrophils, we identified circRNAs in diabetic-derived neutrophils obtained from BKS.Cg-<i>Dock7<sup>m</sup> +/+ Lepr<sup>db</sup></i>/J (<i>Lepr<sup>db/db</sup></i> and <i>Lepr<sup>db/+</sup></i>) mice using microarrays. Neutrophils from pooled bone marrow of three diabetic and three non-diabetic mice were isolated and total RNA was extracted. Microarray analysis was performed using the Arraystar Mouse Circular RNA Array. The results showed that three circRNAs were significantly increased and six circRNAs were significantly decreased in diabetic-derived neutrophils compared with non-diabetic-derived neutrophils. The expressions of some circRNAs in diabetic-derived neutrophils were more than double those in non-diabetic-derived neutrophils. The circRNAs contain binding sites of miRNAs, which were differentially expressed in diabetic-derived neutrophils. Our results suggest that circRNAs may be involved in the regulation of inflammation in diabetic-derived neutrophils.https://www.mdpi.com/2227-9059/10/12/3129diabetic-derived neutrophilcircular RNAmicroRNAinflammationwound healingdiabetes
spellingShingle Takahiro Umehara
Ryoichi Mori
Kimberly A. Mace
Katsumi Tanaka
Noriho Sakamoto
Kazuya Ikematsu
Hiroaki Sato
circRNAs May Be Involved in Dysfunction of Neutrophils of Type 2 Diabetic Mice through Regulation of Specific miRNAs
Biomedicines
diabetic-derived neutrophil
circular RNA
microRNA
inflammation
wound healing
diabetes
title circRNAs May Be Involved in Dysfunction of Neutrophils of Type 2 Diabetic Mice through Regulation of Specific miRNAs
title_full circRNAs May Be Involved in Dysfunction of Neutrophils of Type 2 Diabetic Mice through Regulation of Specific miRNAs
title_fullStr circRNAs May Be Involved in Dysfunction of Neutrophils of Type 2 Diabetic Mice through Regulation of Specific miRNAs
title_full_unstemmed circRNAs May Be Involved in Dysfunction of Neutrophils of Type 2 Diabetic Mice through Regulation of Specific miRNAs
title_short circRNAs May Be Involved in Dysfunction of Neutrophils of Type 2 Diabetic Mice through Regulation of Specific miRNAs
title_sort circrnas may be involved in dysfunction of neutrophils of type 2 diabetic mice through regulation of specific mirnas
topic diabetic-derived neutrophil
circular RNA
microRNA
inflammation
wound healing
diabetes
url https://www.mdpi.com/2227-9059/10/12/3129
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