These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


PUBMED FOR HANDHELDS

Search MEDLINE/PubMed


  • Title: The role of Krüppel-like factor 4 in transforming growth factor-β-induced inflammatory and fibrotic responses in human proximal tubule cells.
    Author: Mreich E, Chen XM, Zaky A, Pollock CA, Saad S.
    Journal: Clin Exp Pharmacol Physiol; 2015 Jun; 42(6):680-6. PubMed ID: 25882815.
    Abstract:
    Krüppel-like factor 4 (KLF4) is known to mitigate inflammation in several cell types. Using human proximal tubule cells, the present study aimed to investigate the role of KLF4 in regulating transforming growth factor (TGF)-β₁ induced inflammatory and fibrotic responses. Human kidney proximal tubular cells were exposed to high glucose, or TGF-β₁ and KLF4 expressions were determined. Cells were then transfected with empty vector or KLF4 and exposed to 2-ng/mL TGF-β₁ for up to 72 h. Inflammatory proteins (macrophage migration inhibitory factor and monocyte chemoattractant protein-1) and pro-fibrotic proteins (fibronectin and collagen IV) were measured after 72 h by enzyme-linked immunosorbent assay and western blot, respectively. To determine the relevance to in vivo models of chronic kidney disease, KLF4 protein expression in streptozotocin-induced diabetic mice was determined. Krüppel-like factor 4 messenger RNA (mRNA) levels were significantly reduced in high glucose-treated human kidney proximal tubular cells. High glucose increased TGF-β₁ mRNA expression, which significantly increased migration inhibitory factor and monocyte chemoattractant protein-1 protein secretion. Transforming growth factor-β₁ significantly increased fibronectin and collagen IV protein expression. The overexpression of KLF4 significantly reduced TGF-β-mediated increases in migration inhibitory factor and monocyte chemoattractant protein-1 but had no effect on TGF-β-mediated fibronectin and collagen IV mRNA and protein expression. The levels of KLF4 mRNA were significantly reduced in the diabetic kidney, and diabetic animals had a significant reduction in renal tubular expression of KLF4 proteins. This data suggest that KLF4 reduces inflammation induced by TGF-β₁, suggesting a therapeutic role for KLF4 in diabetic nephropathy.
    [Abstract] [Full Text] [Related] [New Search]