Cited by 97Connective Tissue Growth Factor ResearchTGF-β signaling in diseasesChronic Kidney Disease and Diabetes

TGF-β1 induces IL-8 and MCP-1 through a connective tissue growth factor-independent pathway

Qi, Weier, Chen, Xinming, Polhill, Tania S., Sumual, Siska, Twigg, Stephen, Gilbert, Richard E., Pollock, Carol A.·2006·American Journal of Physiology-Renal Physiology

Abstract

Transforming growth factor-β 1 (TGF-β 1) functions as an important immunomodulatory cytokine in human kidney. Evidence suggests that connective tissue growth factor (CTGF) is an important downstream mediator of the profibrotic effects of TGF-β 1. However, the role of CTGF in TGF-β 1-induced chemokine production remains unknown. This study was undertaken to determine whether CTGF is involved in mediating TGF-β 1-induced chemokine production in renal proximal tubular (HK-2) cells. Interleukin-8 (IL-8) and macrophage chemoattractant protein-1 (MCP-1) were measured. TGF-β 1 induced an increase in IL-8 and MCP-1 (both P < 0.05) compared with control levels. CTGF was effectively silenced using small interference RNA (siRNA) in HK-2 cells. RT-PCR and real-time PCR confirmed a 94% reduction in CTGF mRNA. In the CTGF-silenced cells, TGF-β 1-stimulated IL-8 and MCP-1 secretion was not altered compared with control cells. Similarly, basal secretion of IL-8 and MCP-1 was not changed in CTGF-silenced cells. The direct effect of CTGF (20, 200, and 400 ng/ml) on IL-8 and MCP-1 was assessed at 24-, 48-, and 72-h time points and no stimulation was observed. Our studies further demonstrate that in the CTGF gene-silenced cells, CTGF partially mediates TGF-β 1-induced fibronectin and collagen IV secretion. These data suggest that TGF-β 1 induced IL-8 and MCP-1 via CTGF-independent pathway. TGF-β mediates both fibrosis and chemokine production in the proximal tubule of the kidney. However, CTGF plays a more specific role as a downstream mediator of TGF-β 1-induced fibrosis.

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Crossref · 10.1152/ajprenal.00254.2005

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  • TGF-β influences CAF expression of cytokines and chemokines that act on cancer, endothelial and/or immune cells, such as HGF, VEGF, IL-6, IL-8, MCP1, PGE2 and CXCL12.

    “Finally, TGF-β influences CAF expression of cytokines and chemokines that act on cancer, endothelial and/or immune cells, such as HGF245, VEGF, IL-6, IL-8, MCP1, PGE2 and CXCL12229,257–262.”

    From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [260]

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Authors
Qi, W., Chen, X., Polhill, T. S., Sumual, S., Twigg, S., Gilbert, R. E., & Pollock, C. A.
Affiliations
  • The University of Sydney (AU)
  • University of Toronto (CA)
Venue
American Journal of Physiology-Renal Physiology
Published
2006-03
Volume
290
Issue
3
Pages
F703-F709
ISSN
  • 1522-1466 (ISSN-L)
  • 1931-857X
OpenAlex
W2145502337
Cited by
97
References
45
Citations by year
2026: 3 · 2025: 2 · 2024: 5 · 2023: 2 · 2022: 10 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 4 · 2013: 10 · 2012: 10
FWCI
2.13
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Renal Physiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
FibroGen
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
Keywords
TGF-β1, connective tissue growth factor, interleukin-8, MCP-1, chemokine production, proximal tubule, HK-2 cells, renal fibrosis, fibronectin, type IV collagen, siRNA knockdown
MeSH terms
Base Sequence, Cell Line, Gene Expression Regulation, Humans, Kidney Tubules, Proximal, Recombinant Proteins, Interleukin-8, Transforming Growth Factor beta, Immediate-Early Proteins, DNA Primers, Chemokine CCL2, RNA, Small Interfering, Intercellular Signaling Peptides and Proteins, Connective Tissue Growth Factor

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