Related Experiment Video

Updated: Aug 8, 2026

Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection
10:15

Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection

Published on: November 10, 2021

Transforming growth factor-beta1 differentially mediates fibronectin and inflammatory cytokine expression in kidney

Weier Qi1, Xinming Chen, John Holian

  • 1Dept. of Medicine, Level 3, Wallace Freeborn Professorial Block, Royal North Shore Hospital, St. Leonards, NSW, Australia.

American Journal of Physiology. Renal Physiology
|May 25, 2006
PubMed

Transforming growth factor-beta(1) (TGF-beta(1)) is not only an important fibrogenic but also immunomodulatory cytokine in the human kidney. We have recently demonstrated that TGF-beta(1) induces interleukin-8 (IL-8), macrophage chemoattractant protein-1 (MCP-1), and fibronectin production in renal proximal tubular (HK-2) cells. However, the unique dependence of IL-8, MCP-1, and fibronectin on TGF-beta(1) expression is unknown. The TGF-beta(1) gene was effectively silenced in HK-2 cells using small-interference (si) RNA. Basal secretion of IL-8 and MCP-1 decreased (both P < 0.05) but, paradoxically, fibronectin increased (P < 0.05) in TGF-beta(1)-silenced cells compared with cells transfected with nonspecific siRNA. Significant increases were observed in mRNA for the TGF-beta(2) (P < 0.05), TGF-beta(3) (P < 0.05) isoforms and pSmad2 (P < 0.05), which were reflected in protein expression. Concurrent exposure to pan-specific TGF-beta antibody reversed the observed increase in fibronectin expression, suggesting that TGF-beta(2) and TGF-beta(3) isoforms mediate the increased fibronectin expression in TGF-beta(1)-silenced cells. An increase in the DNA binding activity of activator protein-1 (AP-1; P < 0.05) was also observed in TGF-beta(1)-silenced cells. In contrast, nuclear factor-kappaB (NF-kappaB) DNA binding activity was significantly decreased (P < 0.0005). These studies demonstrate that TGF-beta(1) is a key regulator of IL-8 and MCP-1, whereas fibronectin expression is regulated by a complex interaction between the TGF-beta isoforms in the HK-2 proximal tubular cell line. Decreased expression of TGF-beta(1) reduces chemokine production in association with reduced NF-kappaB DNA binding activity, suggesting that immunomodulatory pathways in the kidney are specifically dependent on TGF-beta(1). Conversely, decreased expression of TGF-beta(1) results in increased TGF-beta(2), TGF-beta(3), AP-1, and pSmad2 that potentially mediates the observed increase in fibronectin.

More Related Videos

Studying TGF-&#946; Signaling and TGF-&#946;-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-&#946; Signaling07:49

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

Published on: August 3, 2018

Related Concept Videos

TGF - &#946; Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Fibronectins Connect Cells with ECM01:25

Fibronectins Connect Cells with ECM

Fibronectin is an adhesive glycoprotein present in the extracellular matrix of embryogenic and adult tissue. These molecules primarily aid in regulating cell motility and attachment. A fibronectin molecule is composed of two identical polypeptide chains attached to each other by a pair of disulfide bonds at the C-terminal.
Both proteoglycans and collagen are attached to fibronectin proteins, which, in turn, are attached to integrin proteins. These integrin proteins interact with transmembrane...
Introduction to Fibroblasts01:09

Introduction to Fibroblasts

Rudolph Virchow discovered spindle-shaped cells called fibroblasts in 1858. Inactive fibroblasts, called fibrocytes, become activated by various stimuli, such as growth factors and inflammatory cytokines. Activated fibroblasts play a crucial role in wound healing, inflammation, formation of new blood vessels, and cancer progression. Uncontrolled activation of fibroblasts results in fibrosis, the excess deposition of fibrous tissue, which can lead to scarring and affect normal organs. This...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...