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Xu, Tian‐Hua; Qiu, Xiao‐Bo; Sheng, Zi‐Tong; Han, Yi‐Ran; Wang, Jian; Tian, Bin‐Yao; Yao, Li
Journal of cellular physiology, August 2019, 2019-08-00, 20190801, Letnik: 234, Številka: 8Journal Article
Pathological calcification represents an event that consequently leads to a distinct elevation in the morbidity and mortality of patients with chronic kidney disease (CKD) in addition to strengthening its correlation with hyperphosphatemia. Epigenomic regulation by specific microRNAs (miRNAs) is reported to be involved in ectopic calcification. However, the finer molecular mechanisms governing this event remain unclear. Hence, this study aimed to identify the potential miRNAs involved in vascular calcification (VC) development and progression. Initially, mitochondrial membrane potential (MMP), autophagy‐specific markers (LC3II/LC3I and Beclin1) and phenotype‐specific markers of osteoblasts (runt‐related transcription factor 2 and Msx2) were measured to evaluate autophagy and VC in β‐glycerophosphate‐induced vascular smooth muscle cells (VSMCs) with either miR‐30b restoration or miR‐30b knockdown performed in vitro. The VC in vivo was represented by calcified nodule formation in the aorta of the rats undergoing 5/6 nephrectomy followed by a 1.2% phosphorus diet using Alizarin Red staining. SOX9 was verified as the target of miR‐30b according to luciferase activity determination. Restoration of miR‐30b was revealed to markedly diminish the expression of SOX9 while acting to inhibit activation of the mTOR signaling pathway. Knockdown of miR‐30b reduced MMP and autophagy, elevated VC, and suppressed the presence of rapamycin (an inhibitor of the mTOR signaling pathway). In addition, upregulated expression of miR‐30b attenuated VC in vivo. Taken together, the key findings of this study identified the inhibitory role of miR‐30b in VC, presenting an enhanced understanding of miRNA as a therapeutic target to curtail progressive VC in hyperphosphatemia of CKD.
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Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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