07 June 2020 : Laboratory Research
Autophagy Inhibition Sensitizes Renal Tubular Epithelial Cell to G1 Arrest Induced by Transforming Growth Factor beta (TGF-β)
Chen Yang1ACEG, Hong-luan Wu1BCDE, Zhi-hang Li1CDEF, Xiao-cui Chen1BCD, Hong-yong Su1BF, Xiao-yan Guo1CD, Ning An1EFG, Kai-peng Jing1EF, Qing-jun Pan1EF, Hua-feng Liu1ADEFG*DOI: 10.12659/MSM.922673
Med Sci Monit 2020; 26:e922673
Abstract
BACKGROUND: Cell cycle arrest and autophagy have been demonstrated to be involved in various transforming growth factor (TGF)-β-mediated phenotype alterations of tubular epithelial cells (TECs) and tubulointerstitial fibrosis. But the relationship between cell cycle arrest and the autophagy induced by TGF-β has not been explored well.
MATERIAL AND METHODS: The effects of autophagy inhibition on TGF-β-induced cell cycle arrest in TECs were explored in vitro. Human kidney-2 (HK-2) cells were stimulated by TGF-β with or without a combined treatment of autophagy inhibitor chloroquine (CQ) or bafilomycin A1 (Baf).
RESULTS: Autophagy inhibition by CQ or Baf promotes the suppression of growth in TGF-β-treated HK-2 cells, as detected by the Cell Counting Kit-8 (CCK-8) method. In addition, CQ or Baf stimulation enhances G1 arrest in TGF-β treated HK-2 cells, as investigated using propidium iodide (PI) staining and flow cytometry, which was further confirmed by a decrease in the expression of phosphorylated retinoblastoma protein (p-RB) and cyclin-dependent kinase 4 (CDK4). The upregulation of p21 induced by CQ or Baf may mediate an enhanced G1 arrest in TGF-β treated HK-2 cells. Western blot analysis showed that TGF-β-induced expression of extracellular matrix fibronectin was notably upregulated in the presence of autophagy inhibitors.
CONCLUSIONS: Inhibition of autophagy sensitizes the TECs to G1 arrest and proliferation suppression induced by TGF-β that contributes to the induction of tubulointerstitial fibrosis.
Keywords: Fibrosis, G1 Phase Cell Cycle Checkpoints, Transforming Growth Factor beta, Cell Line, Chloroquine, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase Inhibitor p21, Fibronectins, In Vitro Techniques, Kidney Tubules, Macrolides, Renal Insufficiency, Chronic, Retinoblastoma Protein
Editorial
01 April 2024 : Editorial
Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection – Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug ResistanceDOI: 10.12659/MSM.944600
Med Sci Monit 2024; 30:e944600
In Press
08 Mar 2024 : Laboratory Research
Evaluation of Retentive Strength of 50 Endodontically-Treated Single-Rooted Mandibular Second Premolars Res...Med Sci Monit In Press; DOI: 10.12659/MSM.944110
11 Mar 2024 : Clinical Research
Comparison of Effects of Sugammadex and Neostigmine on Postoperative Neuromuscular Blockade Recovery in Pat...Med Sci Monit In Press; DOI: 10.12659/MSM.942773
12 Mar 2024 : Clinical Research
Comparing Neuromuscular Blockade Measurement Between Upper Arm (TOF Cuff®) and Eyelid (TOF Scan®) Using Miv...Med Sci Monit In Press; DOI: 10.12659/MSM.943630
11 Mar 2024 : Clinical Research
Enhancement of Frozen-Thawed Human Sperm Quality with Zinc as a Cryoprotective AdditiveMed Sci Monit In Press; DOI: 10.12659/MSM.942946
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952