Osteogenic Differentiation of Renal Interstitial Fibroblasts Promoted by lncRNA MALAT1 May Partially Contribute to Randall's Plaque Formation.
Osteogenic Differentiation of Renal Interstitial Fibroblasts Promoted by lncRNA MALAT1 May Partially Contribute to Randall's Plaque Formation.
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lncRNA MALAT1促进肾间质成纤维细胞的成骨分化可能部分促进兰德尔斑块的形成
DOI：
10.3389/fcell.2020.596363
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发表时间：
2020
影响因子：
5.5
通讯作者：
Chen H
中科院分区：
文献类型：
--
作者：
Zhu Z;Huang F;Xia W;Zeng H;Gao M;Li Y;Zeng F;He C;Chen J;Chen Z;Li Y;Cui Y;Chen H
目前认为兰德尔斑（RP）构成了特发性草酸钙结石形成的病灶，但 RP 形成的上游事件仍不清楚。本研究旨在探讨 RP 形成是否与生物矿化具有相似性，并阐明 lncRNA MALAT1 在人肾间质成纤维细胞 (hRIF) 成骨分化中的潜在作用。在 RP 中评估生物矿化和 MALAT1 表达，并在成骨条件下分离和诱导 hRIF 以进行进一步实验。 MALAT1 中的转录起始和终止位点通过 5' 和 3' RACE 进行鉴定。 RNA 免疫沉淀测定和荧光素酶测定用于验证 MALAT1、Runx2 和 miRNA 之间的相互作用。在用成骨培养基诱导的 RP 和 hRIF 中观察到成骨标志物和 MALAT1 表达上调。通过电子显微镜进一步验证了诱导 hRIF 中 RP 的生物矿化和磷酸钙 (CaP) 沉积物。此外，MALAT1 的过表达促进了 hRIF 的成骨表型，而用 miR-320a-5p 模拟物治疗和 Runx2 敲低则显着抑制了成骨表型。进一步分析表明，MALAT1 作为竞争性内源 RNA 来海绵 miR-320a-5p，导致 Runx2 上调，从而促进 hRIF 的成骨分化。异位钙化和 MALAT1 部分促进了 RP 的形成，其中 MALAT1 可能促进 Runx2 表达，通过海绵 miRNA-320a-5p 来调节 hRIF 的成骨分化。目前的研究通过成骨样细胞驱动的过程，为 lncRNA 引导的 RP 形成机制提供了新的线索。
The current belief is that Randall’s plaques (RP) constitute a nidus for the formation of idiopathic calcium oxalate stones, but the upstream events in RP formation remain unclear. The present study aimed to investigate whether RP formation shares similarities with biomineralization and to illustrate the potential role played by the lncRNA MALAT1 in osteogenic differentiation of human renal interstitial fibroblasts (hRIFs). Biomineralization and MALAT1 expression were assessed in RP, and hRIFs were isolated and induced under osteogenic conditions for further experiments. The transcription initiation and termination sites in MALAT1 were identified by 5′ and 3′ RACE. RNA immunoprecipitation assays and luciferase assays were used to validate the interactions among MALAT1, Runx2 and miRNAs. Upregulated expression of osteogenic markers and MALAT1 was observed in RP and hRIFs induced with osteogenic medium. Biomineralization in RP and calcium phosphate (CaP) deposits in induced hRIFs were further verified by electron microscopy. Furthermore, overexpression of MALAT1 promoted the osteogenic phenotype of hRIFs, while treatment with a miR-320a-5p mimic and knockdown of Runx2 significantly suppressed the osteogenic phenotype. Further analysis showed that MALAT1 functioned as a competing endogenous RNA to sponge miR-320a-5p, leading to upregulation of Runx2 and thus promoting osteogenic differentiation of hRIFs. Ectopic calcification and MALAT1 partially contributed to the formation of RP, in which MALAT1 might promote Runx2 expression to regulate osteogenic differentiation of hRIFs by sponging miRNA-320a-5p. The current study sheds new light on the lncRNA-directed mechanism of RP formation via a process driven by osteogenic-like cells.
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影响因子：
3.1
作者：
Evan AP;Worcester EM;Coe FL;Williams J Jr;Lingeman JE
通讯作者：
Lingeman JE
影响因子：
56.9
作者：
Kapranov, Philipp;Cheng, Jill;Gingeras, Thomas R.
通讯作者：
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影响因子：
4
作者：
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通讯作者：
Chen, Xiaodong
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影响因子：
5.6
作者：
Chen, Jie;Zhang, Di;Tang, Xiao-Jing
通讯作者：
Tang, Xiao-Jing
影响因子：
3.4
作者：
He, Deng;Wang, Shaogang;Qin, Baolong
通讯作者：
Qin, Baolong