Inhibition of cytokine-like protein 1 transcription hinders wound-healing process in diabetic rats.

IF 3.2 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Diabetic Medicine Pub Date : 2024-11-05 DOI:10.1111/dme.15459
Jie Xu, Yun Tong, Manman Lin, Zikai Zhang, Tian Li, Fan Zhang
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Abstract

Aim: This study explored the function and mechanism of cytokine-like protein 1 (CYTL1) in regulating the wound-healing process of rats with diabetes mellitus (DM).

Methods: A wound was made in diabetic rats, in which CYTL1 overexpression or HDAC1 expression-interfering adenovirus was injected. The wound area on day 0, 7, 14 and 21 was observed and photographed to calculate the wound-healing rate. The wound tissues were collected for H&E, Masson staining and CD31 immunohistochemistry. The HDAC1 and CYTL1 mRNA and protein expressions in wound tissues were detected by RT-qPCR and western blot. The regulation of HDAC1 on CYTL1 was predicted by hTFtarget and AnimalTFDB database. The H3K27Ac level in the CYTL1 promoter was detected by chromatin immunoprecipitation (ChIP).

Results: Diabetic rats with CYTL1 overexpression or interfered HDAC1 expression had accelerated the wound-healing rate, in which massive fibroblasts, attenuated inflammatory infiltration and increased collagen and microvessel density were observed. Further experiments found that HDAC1 can inhibit CYTL1 transcription and expression by inhibiting H3K27Ac expression in CYTL1 promoter.

Conclusion: Collected evidence showed HDAC1 can inhibit CYTL1 transcription by down-regulating the H3K27Ac level in CYTL1 promoter to slow down the wound-healing process in diabetic ulcer rats.

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抑制细胞因子样蛋白 1 的转录会阻碍糖尿病大鼠的伤口愈合过程。
目的:本研究探讨了细胞因子样蛋白1(CYTL1)在调节糖尿病(DM)大鼠伤口愈合过程中的功能和机制:方法:给糖尿病大鼠伤口注射CYTL1过表达或HDAC1表达干扰腺病毒。观察并拍摄第 0、7、14 和 21 天的伤口面积,计算伤口愈合率。收集伤口组织进行 H&E、Masson 染色和 CD31 免疫组化。通过 RT-qPCR 和 western blot 检测伤口组织中 HDAC1 和 CYTL1 的 mRNA 和蛋白表达。hTFtarget和AnimalTFDB数据库预测了HDAC1对CYTL1的调控作用。染色质免疫沉淀(ChIP)检测了CYTL1启动子中的H3K27Ac水平:结果:CYTL1过表达或HDAC1表达受干扰的糖尿病大鼠伤口愈合速度加快,观察到大量成纤维细胞,炎症浸润减轻,胶原蛋白和微血管密度增加。进一步的实验发现,HDAC1 可以通过抑制 CYTL1 启动子中 H3K27Ac 的表达来抑制 CYTL1 的转录和表达:收集的证据表明,HDAC1可通过下调CYTL1启动子中的H3K27Ac水平来抑制CYTL1的转录,从而延缓糖尿病溃疡大鼠的伤口愈合过程。
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来源期刊
Diabetic Medicine
Diabetic Medicine 医学-内分泌学与代谢
CiteScore
7.20
自引率
5.70%
发文量
229
审稿时长
3-6 weeks
期刊介绍: Diabetic Medicine, the official journal of Diabetes UK, is published monthly simultaneously, in print and online editions. The journal publishes a range of key information on all clinical aspects of diabetes mellitus, ranging from human genetic studies through clinical physiology and trials to diabetes epidemiology. We do not publish original animal or cell culture studies unless they are part of a study of clinical diabetes involving humans. Categories of publication include research articles, reviews, editorials, commentaries, and correspondence. All material is peer-reviewed. We aim to disseminate knowledge about diabetes research with the goal of improving the management of people with diabetes. The journal therefore seeks to provide a forum for the exchange of ideas between clinicians and researchers worldwide. Topics covered are of importance to all healthcare professionals working with people with diabetes, whether in primary care or specialist services. Surplus generated from the sale of Diabetic Medicine is used by Diabetes UK to know diabetes better and fight diabetes more effectively on behalf of all people affected by and at risk of diabetes as well as their families and carers.”
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