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SERPINH1, Targeted by miR-29b, Modulated Proliferation and Migration of Human Retinal Endothelial Cells Under High Glucose Conditions
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy ( IF 2.8 ) Pub Date : 2021-08-04 , DOI: 10.2147/dmso.s307771
Lingfei Hu 1 , Yinping Liu 1 , Chaobing Wei 1 , Huixiang Jin 1 , Lixin Mei 1 , Changfan Wu 1
Affiliation  

Aim: In the present study, we performed bioinformatics studies and in vitro functional assays to explore the underlying role of serpin family H member 1 (SERPINH1) in the diabetic retinopathy.
Methods: Common differentially expressed genes (DEGs) between diabetic retinal tissues and normal retinal tissues were analyzed using Gene Expression Omnibus (GEO) database. The proliferation and migration of human retinal endothelial cells (HRECs) was evaluated by MTS, EdU and wound healing assays, respectively; the miRNA and mRNAs expression levels of hub genes in HRECs were determined using quantitative real-time PCR (qRT-PCR). Protein levels were determined using a Western blot assay.
Results: A total of 189 common DEGs were screened between two GEO datasets (GSE60436 and GSE94019), and ten potential hub genes that may link to the progression of diabetic retinopathy were detected. The qRT-PCR results showed that collagen, type I, alpha 1 (COL1A1), Collagen, type I, alpha 2 (COL1A2) and serpin family H member 1 (SERPINH1) mRNA expression levels were up-regulated in the HRECs after being exposed to high glucose for 48 h. Silence of SERPINH1 repressed the high glucose-induced increase in proliferation and migration of HRECs. SERPINH1 was a target of miR-29b and was suppressed by miR-29 in HRECs. SERPINH1 overexpression promoted HREC proliferation and migration. Furthermore, miR-29b suppressed HREC proliferation and migration under high-glucose stimulation, which was significantly attenuated by enforced expression of SERPINH1.
Conclusion: In conclusion, by performing the integrated bioinformatics analysis, the present study suggested that 3 hub genes (COL1A1, COL1A2 and SERPINH1) may be associated with diabetic retinopathy pathophysiology. Further mechanistic studies indicated that miR-29b/SERPINH1 signaling participated in high glucose-induced enhancement in the proliferation and migration of HRECs.

Keywords: diabetic retinopathy, bioinformatics analysis, HRECs, SERPINH1, proliferation, migration


中文翻译:

SERPINH1,由 miR-29b 靶向,在高糖条件下调节人视网膜内皮细胞的增殖和迁移

目的:在本研究中,我们进行了生物信息学研究和体外功能测定,以探索丝氨酸蛋白酶抑制剂家族 H 成员 1 (SERPINH1) 在糖尿病视网膜病变中的潜在作用。
方法:使用基因表达综合(GEO)数据库分析糖尿病视网膜组织和正常视网膜组织之间的常见差异表达基因(DEGs)。分别通过 MTS、EdU 和伤口愈合试验评估人视网膜内皮细胞 (HREC) 的增殖和迁移;使用定量实时 PCR (qRT-PCR) 测定 HRECs 中枢纽基因的 miRNA 和 mRNAs 表达水平。使用蛋白质印迹测定法测定蛋白质水平。
结果:在两个 GEO 数据集(GSE60436 和 GSE94019)之间共筛选了 189 个常见 DEG,并检测到了 10 个可能与糖尿病视网膜病变进展相关的潜在枢纽基因。qRT-PCR结果显示胶原蛋白I型α1(COL1A1)胶原蛋白I型α2(COL1A2)和丝氨酸蛋白酶抑制剂家族H成员1(SERPINH1)mRNA表达水平在HRECs暴露后上调高糖48小时。SERPINH1 的沉默抑制了高糖诱导的 HRECs 增殖和迁移的增加。SERPINH1 是 miR-29b 的靶标,在 HRECs 中被 miR-29 抑制。SEPINH1 过表达促进 HREC 增殖和迁移。此外,在高葡萄糖刺激下,miR-29b 抑制 HREC 增殖和迁移,这通过 SERPINH1 的强制表达显着减弱。
结论:综上所述,通过综合生物信息学分析,本研究表明 3 个中枢基因(COL1A1、COL1A2 和 SERPINH1)可能与糖尿病视网膜病变的病理生理学相关。进一步的机制研究表明,miR-29b/SERPINH1 信号通路参与了高糖诱导的 HRECs 增殖和迁移增强。

关键词:糖尿病视网膜病变,生物信息学分析,HRECs,SERPINH1,增殖,迁移
更新日期:2021-08-03
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