当前位置：
X-MOL 学术
›
Drug Des. Dev. Ther.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
LncRNA PVT1 Suppresses the Progression of Renal Fibrosis via Inactivation of TGF-β Signaling Pathway.
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2020-08-26 , DOI: 10.2147/dddt.s245244 Lu Cao 1 , Peng Qin 2 , Jianjiang Zhang 1 , Huiju Qiao 1 , Peipei Shi 1 , Huali Huo 1
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2020-08-26 , DOI: 10.2147/dddt.s245244 Lu Cao 1 , Peng Qin 2 , Jianjiang Zhang 1 , Huiju Qiao 1 , Peipei Shi 1 , Huali Huo 1
Affiliation
Background: Renal fibrosis is a frequent pathway leading to end-stage kidney dysfunction. In addition, renal fibrosis is the ultimate manifestation of chronic kidney diseases (CKD). Long noncoding RNAs (lncRNAs) are known to be involved in occurrence of renal fibrosis, and lncRNA plasmacytoma variant translocation 1 (PVT1) has been reported to act as a key biomarker in renal diseases. However, the role of PVT1 in renal fibrosis remains unclear.
Materials and Methods: HK-2 cells were treated with TGF-β 1 to mimic renal fibrosis in vitro. Gene and protein expressions in HK-2 cells were measured by qRT-PCR and Western-blot, respectively. ELISA was used to test the level of creatinine (CR) and blood urea nitrogen (BUN) in serum of mice. Additionally, unilateral ureteral obstruction (UUO)-induced renal fibrosis mice model was established to investigate the effect of PVT1 on renal fibrosis in vivo.
Results: PVT1 was upregulated in TGF-β 1-treated HK-2 cells. In addition, TGF-β 1-induced upregulation of α-SMA and fibronectin in HK-2 cells was significantly reversed by PVT1 knockdown. Meanwhile, PVT1 bound to miR-181a-5p in HK-2 cells. Moreover, miR-181a-5p directly targeted TGF-βR1. Furthermore, miR-181a-5p antagonist could significantly reverse the anti-fibrotic effect of PVT1 knockdown. Besides, knockdown of PVT1 notably attenuated the symptom of renal fibrosis in vivo.
Conclusion: Knockdown of PVT1 significantly inhibited the progression of renal fibrosis in vitro and in vivo. Thus, PVT1 may serve as a potential target for the treatment of renal fibrosis.
中文翻译：
LncRNA PVT1 通过灭活 TGF-β 信号通路抑制肾纤维化的进展。
背景：肾纤维化是导致终末期肾功能障碍的常见途径。此外，肾纤维化是慢性肾脏病（CKD）的最终表现。已知长链非编码 RNA (lncRNA) 与肾纤维化的发生有关，据报道，lncRNA 浆细胞瘤变体易位 1 (PVT1) 是肾脏疾病的关键生物标志物。然而，PVT1在肾纤维化中的作用仍不清楚。
材料和方法：用 TGF-β 1 处理 HK-2 细胞以在体外模拟肾纤维化。分别通过qRT-PCR和Western-blot测量HK-2细胞中的基因和蛋白表达。采用ELISA法检测小鼠血清中肌酐(CR)和血尿素氮(BUN)的水平。此外，建立单侧输尿管梗阻（UUO）诱导的肾纤维化小鼠模型，以研究PVT1对体内肾纤维化的影响。
结果： PVT1 在 TGF-β 1 处理的 HK-2 细胞中上调。此外，PVT1 敲低可显着逆转 HK-2 细胞中 TGF-β 1 诱导的 α-SMA 和纤连蛋白上调。同时，PVT1 在 HK-2 细胞中与 miR-181a-5p 结合。此外，miR-181a-5p直接靶向TGF-βR1。此外，miR-181a-5p拮抗剂可以显着逆转PVT1敲低的抗纤维化作用。此外，PVT1的敲低显着减轻了体内肾纤维化的症状。
结论： PVT1的敲低可显着抑制体外和体内肾纤维化的进展。因此，PVT1可能作为治疗肾纤维化的潜在靶点。
更新日期：2020-08-26
Materials and Methods: HK-2 cells were treated with TGF-β 1 to mimic renal fibrosis in vitro. Gene and protein expressions in HK-2 cells were measured by qRT-PCR and Western-blot, respectively. ELISA was used to test the level of creatinine (CR) and blood urea nitrogen (BUN) in serum of mice. Additionally, unilateral ureteral obstruction (UUO)-induced renal fibrosis mice model was established to investigate the effect of PVT1 on renal fibrosis in vivo.
Results: PVT1 was upregulated in TGF-β 1-treated HK-2 cells. In addition, TGF-β 1-induced upregulation of α-SMA and fibronectin in HK-2 cells was significantly reversed by PVT1 knockdown. Meanwhile, PVT1 bound to miR-181a-5p in HK-2 cells. Moreover, miR-181a-5p directly targeted TGF-βR1. Furthermore, miR-181a-5p antagonist could significantly reverse the anti-fibrotic effect of PVT1 knockdown. Besides, knockdown of PVT1 notably attenuated the symptom of renal fibrosis in vivo.
Conclusion: Knockdown of PVT1 significantly inhibited the progression of renal fibrosis in vitro and in vivo. Thus, PVT1 may serve as a potential target for the treatment of renal fibrosis.
中文翻译：
LncRNA PVT1 通过灭活 TGF-β 信号通路抑制肾纤维化的进展。
背景：肾纤维化是导致终末期肾功能障碍的常见途径。此外，肾纤维化是慢性肾脏病（CKD）的最终表现。已知长链非编码 RNA (lncRNA) 与肾纤维化的发生有关，据报道，lncRNA 浆细胞瘤变体易位 1 (PVT1) 是肾脏疾病的关键生物标志物。然而，PVT1在肾纤维化中的作用仍不清楚。
材料和方法：用 TGF-β 1 处理 HK-2 细胞以在体外模拟肾纤维化。分别通过qRT-PCR和Western-blot测量HK-2细胞中的基因和蛋白表达。采用ELISA法检测小鼠血清中肌酐(CR)和血尿素氮(BUN)的水平。此外，建立单侧输尿管梗阻（UUO）诱导的肾纤维化小鼠模型，以研究PVT1对体内肾纤维化的影响。
结果： PVT1 在 TGF-β 1 处理的 HK-2 细胞中上调。此外，PVT1 敲低可显着逆转 HK-2 细胞中 TGF-β 1 诱导的 α-SMA 和纤连蛋白上调。同时，PVT1 在 HK-2 细胞中与 miR-181a-5p 结合。此外，miR-181a-5p直接靶向TGF-βR1。此外，miR-181a-5p拮抗剂可以显着逆转PVT1敲低的抗纤维化作用。此外，PVT1的敲低显着减轻了体内肾纤维化的症状。
结论： PVT1的敲低可显着抑制体外和体内肾纤维化的进展。因此，PVT1可能作为治疗肾纤维化的潜在靶点。
京公网安备 11010802027423号