MicroRNAs (miRNAs) comprise of a novel class of endogenous small noncoding RNAs that frequently downregulate the expression of target genes. Recent reports suggest that miRNA-200b prevents epithelial-to-mesenchymal transition (EMT) in cancer cells by targeting the E-box binding transcription factors Zinc finger E-box-binding homeobox 1 (ZEB1) and Zinc finger E-box-binding homeobox 2 (ZEB2). About 35% of active fibroblasts are derived from EMT which is central to the development of progressive renal fibrosis. Hence, this study was designed to assess the effect of miRNA-200b on transforming growth factor-β (TGF-β1)-induced fibrotic responses in renal tubular cells. Morphologically, human kidney-2 cells transfected with miRNA-200b retained their epithelial cell characteristics when exposed to TGF-β1. miRNA-200b significantly increased E-cadherin (P < 0.001) and reduced fibronectin mRNA and protein expression (both P < 0.01) independent of phospho-Smad2/3 and phospho-p38 and p42/44 signaling. Increased E-cadherin expression was associated with decreased expression of ZEB1 and ZEB2 and repression of fibronectin was mediated through direct targeting of the fibronectin mRNA, demonstrated using pMIR luciferase reporter assay and site-directed mutagenesis. These results suggest that miRNA-200b suppresses TGF-β1-induced EMT via inhibition of ZEB1 and ZEB2 and the extracellular matrix protein fibronectin by directing targeting of its 3'UTR mRNA, independent of pathways directly involved in TGF-β1 signaling.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1152/ajprenal.00302.2012 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
UHRF1 promotes epithelial-mesenchymal transition mediating renal fibrosis by activating the TGF-β/SMAD signaling pathway.
Sci Rep
January 2025
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
Renal fibrosis is widely recognized as the ultimate outcome of many chronic kidney diseases. The process of epithelial-mesenchymal transition (EMT) plays a critical role in the progression of fibrosis following renal injury. UHRF1, as a critical epigenetic regulator, may play an essential role in the pathogenesis and progression of renal fibrosis and EMT.
View Article and Find Full Text PDFKAT2B inhibits proliferation and invasion via inactivating TGF-β/Smad3 pathway-medicated autophagy and EMT in epithelial ovarian cancer.
Sci Rep
January 2025
Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, People's Republic of China.
Lysine acetyltransferase 2B (KAT2B) plays a crucial role in epigenetic regulation and tumor pathogenesis. Our study investigates KAT2B's function in epithelial ovarian cancer (EOC) using in vivo and in vitro methods. Immunohistochemistry showed the KAT2B expression in EOC tissues.
View Article and Find Full Text PDFFacile integration of a binary nano-prodrug with αPD-L1 as a translatable technology for potent immunotherapy of TNBC.
Acta Biomater
January 2025
Hengyang Medical School, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science, MOE Key Lab of Rare Pediatric Disease, University of South China, Hengyang 421001, China. Electronic address:
Immune checkpoint blockers (ICBs)-based immunotherapy is a favorable approach for efficient triple-negative breast cancer (TNBC) treatment. However, the therapeutic efficacy of ICBs is greatly compromised by immunosuppressive tumor microenvironments (TMEs) and low expression levels of programmed cell death ligand-1 (PD-L1). Herein, we constructed an amphiphilic prodrug by linking a hydrophobic STING agonist, MSA-2 and a hydrophilic chemotherapeutic drug, gemcitabine (GEM) via an ester bond, which can self-assemble into GEM-MSA-2 (G-M) nanoparticles (NPs) with a tumor growth inhibition (TGI) value of 87.
View Article and Find Full Text PDFIntroduction: To determine the effects of atorvastatin on cardiac function and hemodynamics and to investigate its functional mechanism on cardiac fibrosis in acute myocardial infarction (AMI) rats.
Methods: Cardiac functions and hemodynamic changes were evaluated in each group on day 28. Quantitative reverse transcription-polymerase chain reaction, Western blot, and immunohistochemistry were performed to detect the expression of notch1, transforming growth factor-β (TGF-β), Smad2, Smad7, as well as myocardial fibrosis factors (i.
The cellular response of lipopolysaccharide-induced inflammation in keratoconus human corneal fibroblasts to RB-PDT: Insights into cytokines, chemokines and related signaling pathways.
PLoS One
January 2025
Dr. Rolf M. Schwiete Center for Limbal Stem Cell and Aniridia Research, Saarland University, Homburg/Saar, Germany.
Purpose: Rose Bengal Photodynamic Therapy (RB-PDT) offers dual therapeutic benefits by enhancing corneal stiffness and providing antibacterial activity, presenting significant potential for patients with keratoconus complicated by keratitis. Our purpose was to assess the effect of rose bengal photodynamic therapy (RB-PDT) on the expression of pro-inflammatory cytokines and chemokines, as well as on extracellular matrix (ECM)-related molecules, in lipopolysaccharide (LPS)-induced inflammation of keratoconus human corneal fibroblasts (KC-HCFs). Additionally, the involvement of the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways which are downstream of the Toll-like receptor 4 (TLR4) pathway were examined.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!