Bai R, Zhao A-Q, Zhao Z-Q, Liu W-L, Jian D-M
Department of Pediatric Orthopedics, The Second Affiliated Hospital of Inner Mongolia Medical University, Mongolia, China.
Eur Rev Med Pharmacol Sci. 2015 Feb;19(4):545-51.
The chondrocytes, the resident cells of cartilage, are maintained and take effects in the whole life upon chronic hypoxic exposure, which hypoxia-inducible factor 1 alpha (HIF-1α) play pivotal roles in response to. Dysregulation of some microRNA (miRNAs) have also been identified to be involved in hypoxia-related physiologic and pathophysiologic responses in some tissues or cell lines. However, the mechanism of miRNAs reponse to hypoxia remain largely unknown in chondrocytes, including the microRNA-195 (miR-195). AIM To investigate the effects of microRNAs (miRNAs) and hypoxia-inducible factor 1 alpha (HIF-1α) on chondrocytes in physiologic environment.
We compared the expression of miR-195 and HIF-1α mRNA on hypoxia with that on normoxia in ATDC 5 cells by qRT-PCR. Further experiments was performed to confirmed the relationships of miR-195 and HIF-1α by bioinformatics analysis and dual reporter gene assay. we also assessed the effect of miR-195 on apoptosis in hypoxic ATDC 5 cells by transfect with miR-195 mimics.
It was found the downregulated miR-195 and upregulated HIF-1α were present in hypoxic ATDC 5 cells. miR-195 negatively regulated HIF-1α by targeting its 3'-untranslated region. Moreover, the founding indicated miR-195 greatly increased apoptosis and downregulated HIF-1α mRNA occurred simultaneously in hypoxic chondrocytes.
We concluded that miR-195 induced apoptosis in hypoxic chondrocytes by directly targeting HIF-1α.
软骨细胞作为软骨的驻留细胞,在长期低氧暴露下会终生维持并发挥作用,其中缺氧诱导因子1α(HIF-1α)在这一过程中起关键作用。一些微小RNA(miRNA)的失调也被证实参与了某些组织或细胞系中与缺氧相关的生理和病理生理反应。然而,在软骨细胞中,miRNA对缺氧的反应机制,包括微小RNA-195(miR-195),仍基本未知。目的是研究微小RNA(miRNA)和缺氧诱导因子1α(HIF-1α)在生理环境中对软骨细胞的影响。
我们通过qRT-PCR比较了ATDC 5细胞在低氧和常氧条件下miR-195和HIF-1α mRNA的表达。通过生物信息学分析和双荧光素酶报告基因检测进一步实验,以证实miR-195与HIF-1α的关系。我们还通过转染miR-195模拟物评估了miR-195对低氧ATDC 5细胞凋亡的影响。
发现在低氧的ATDC 5细胞中miR-195表达下调,HIF-1α表达上调。miR-195通过靶向HIF-1α的3'-非翻译区对其进行负调控。此外,研究结果表明,在低氧软骨细胞中,miR-195显著增加凋亡的同时HIF-1α mRNA表达下调。
我们得出结论,miR-195通过直接靶向HIF-1α诱导低氧软骨细胞凋亡。