Inhibitory effect of ethyl acetate extract of Aristolochia yunnanensis on cardiac fibrosis through extracellular signal-regulated kinases 1/2 and transforming growth factor β/small mother against decapentaplegic signaling pathways

Regulation by transforming growth factor (TGF)-β plays an important role in immune homeostasis. TGF-β inhibits T cell functions by blocking both proliferation and differentiation. Here we show that TGF-β blocks Th1 differentiation by inhibiting the expression of T-bet, the apparent masterregulator of T helper (Th)1 differentiation. Restoration of T-bet expression through retroviral transduction of T-bet into developing Th1 cells abrogated the inhibitory effect of TGF-β. In addition, we show that, contrary to prior suggestions, downregulation of interleukin 12 receptor β2 chain is not key to the TGF-β–mediated effect. Furthermore, we show that the direct inhibitory effect of TGF-β on T cells is responsible, at least in part, for the inability of BALB/c mice to mount a Leishmania-specific Th1 response and to clear Leishmanial infection.

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(+)-Isobicyclogermacrenal and spathulenol from Aristolochia yunnanensis alleviate cardiac fibrosis by inhibiting transforming growth factor β /small mother against decapentaplegic signaling pathway

Phytotherapy Research ◽

10.1002/ptr.6219 ◽

2018 ◽

Vol 33 (1) ◽

pp. 214-223 ◽

Cited By ~ 6

Author(s):

Lan-Lan Lou ◽

Wei Li ◽

Bin-Hua Zhou ◽

Lin Chen ◽

Han-Zhuang Weng ◽

...

Keyword(s):

Growth Factor ◽

Signaling Pathway ◽

Cardiac Fibrosis ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β

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Proteinase-activated Receptor-2 Transactivation of Epidermal Growth Factor Receptor and Transforming Growth Factor-β Receptor Signaling Pathways Contributes to Renal Fibrosis

Journal of Biological Chemistry ◽

10.1074/jbc.m113.492793 ◽

2013 ◽

Vol 288 (52) ◽

pp. 37319-37331 ◽

Cited By ~ 52

Author(s):

Hyunjae Chung ◽

Rithwik Ramachandran ◽

Morley D. Hollenberg ◽

Daniel A. Muruve

Keyword(s):

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Signaling Pathways ◽

Renal Fibrosis ◽

Transforming Growth Factor ◽

Growth Factor Receptor ◽

Transforming Growth Factor Β ◽

Epidermal Growth ◽

Β Receptor

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Serum-stimulated α1 type IV collagen gene transcription is mediated by TGF-β and inhibited by estradiol

AJP Renal Physiology ◽

10.1152/ajprenal.1998.274.2.f252 ◽

1998 ◽

Vol 274 (2) ◽

pp. F252-F258 ◽

Cited By ~ 11

Author(s):

Jun Lei ◽

Sharon Silbiger ◽

Fuad N. Ziyadeh ◽

Joel Neugarten

Keyword(s):

Growth Factor ◽

Gene Transcription ◽

Type Iv Collagen ◽

Transforming Growth Factor ◽

Combined Treatment ◽

Calf Serum ◽

Neutralizing Antibody ◽

Transforming Growth Factor Β ◽

Inhibitory Effect ◽

Type Iv

We examined the hypothesis that fetal calf serum (FCS) stimulates murine mesangial cell α1 type IV collagen ( COL4A1) gene transcription by increasing autocrine production of transforming growth factor-β (TGF-β) through a platelet-derived growth factor (PDGF)-dependent mechanism. PDGF-stimulated COL4A1 gene transcription was inhibited by neutralizing antibody to TGF-β (119.3 ± 3.6 vs. 106.0 ± 6.2 relative luciferase units, expressed as a percentage of control untreated cells, P < 0.003). FCS-stimulated gene transcription was inhibited by neutralizing antibody to PDGF (148.3 ± 4.1 vs. 136.7 ± 0.3 relative luciferase units, P < 0.002) and by neutralizing antibody to TGF-β (148.3 ± 4.1 vs. 127.1 ± 3.4 relative luciferase units, P < 0.036). The inhibitory effect of combined treatment with anti-PDGF and anti-TGF-β antibody on gene transcription was no greater than that of anti-TGF-β antibody alone [129.5 ± 0.53 vs. 127.1 ± 3.4 relative luciferase units, P = not significant (NS)]. FCS-stimulated gene transcription was also inhibited by estradiol (10−7 M) (148.4 ± 3.1 vs. 119.4 ± 8.1 relative luciferase units, P < 0.019). In the presence of estradiol, anti-TGF-β antibody failed to further reduce serum-stimulated gene transcription (119.4 ± 8.1 vs. 115.6 ± 9.8, P = NS), suggesting that estradiol reverses FCS-stimulated COL4A1 gene transcription by antagonizing the actions of TGF-β. Measurement of type IV collagen synthesis by Western blotting confirmed that the intact gene responded in a manner analogous to the promoter construct.

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