Drug Design, Development and Therapy (Aug 2020)

LncRNA PVT1 Suppresses the Progression of Renal Fibrosis via Inactivation of TGF-β Signaling Pathway

  • Cao L,
  • Qin P,
  • Zhang J,
  • Qiao H,
  • Shi P,
  • Huo H

Journal volume & issue
Vol. Volume 14
pp. 3547 – 3557

Abstract

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Lu Cao,1 Peng Qin,2 Jianjiang Zhang,1 Huiju Qiao,1 Peipei Shi,1 Huali Huo1 1Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, People’s Republic of China; 2Department of Cancer Immunotherapy, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450000, People’s Republic of ChinaCorrespondence: Lu Cao Email [email protected]: 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.Keywords: PVT1, renal fibrosis, miR-181a-5p, TGF-βR1

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