Altered Gene Expression Profiles in the Lungs of Streptozotocin-induced Diabetic Mice.

Development & reproduction Pub Date : 2020-09-01 Epub Date: 2020-09-30 DOI:10.12717/DR.2020.24.3.197
Jung-Hyun Kim, Roya Rasaei, Sujin Park, Ji-Young Kim, Sunghun Na, Seok-Ho Hong
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Abstract

Diabetes mellitus is a common heterogeneous metabolic disorder, characterized by deposition of extracellular matrix, oxidative stress, and vascular dysfunction, thereby leading to gradual loss of function in multiple organs. However, little attention has been paid to gene expression changes in the lung under hyperglycemic conditions. In this study, we found that diabetes inuced histological changes in the lung of streptozotocin-induced diabetic mice. Global gene expression profiling revealed a set of genes that are up- and down-regulated in the lung of diabetic mice. Among these, expression of Amigo2, Adrb2, and Zbtb16 were confirmed at the transcript level to correlate significantly with hyperglycemia in the lung. We further evaluated the effect of human umbilical cord-derived perivascular stem cells (PVCs) on these gene expression in the lung of diabetic mice. Our results show that administration of PVC-conditioned medium significantly suppressed Amig2, Adrb2, and Zbtb16 upregulation in these mice, suggesting that these genes may be useful indicators of lung injury during hyperglycemia. Furthermore, PVCs offer a promising alternative cell therapy for treating diabetic complications via regulation of gene expression.

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链脲佐菌素诱导的糖尿病小鼠肺部基因表达谱的改变。
糖尿病是一种常见的异质性代谢紊乱,以细胞外基质沉积、氧化应激和血管功能障碍为特征,导致多器官功能逐渐丧失。然而,在高血糖条件下,肺中基因表达的变化很少受到关注。在本研究中,我们发现糖尿病引起链脲佐菌素诱导的糖尿病小鼠肺部组织学改变。全球基因表达谱揭示了一组在糖尿病小鼠肺中上调和下调的基因。其中,Amigo2、Adrb2和Zbtb16的表达在转录水平上被证实与肺部高血糖有显著相关。我们进一步评估了人脐带源性血管周围干细胞(PVCs)对糖尿病小鼠肺中这些基因表达的影响。我们的研究结果表明,在这些小鼠中,给予pvc条件培养基显著抑制Amig2、Adrb2和Zbtb16的上调,这表明这些基因可能是高血糖期间肺损伤的有用指标。此外,通过调控基因表达,室性早搏为治疗糖尿病并发症提供了一种有前景的替代细胞疗法。
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