التفاصيل البيبلوغرافية
| العنوان: |
Fibrosis in PCLS: comparing TGF-β and fibrotic cocktail. |
| المؤلفون: |
Machahua, Carlos1,2 (AUTHOR) carlosesteban.machahuahuamani@insel.ch, Marti, Thomas M.3,4 (AUTHOR), Dorn, Patrick3,4 (AUTHOR), Funke-Chambour, Manuela1,2 (AUTHOR) |
| المصدر: |
Respiratory Research. 1/28/2025, Vol. 26 Issue 1, p1-7. 7p. |
| مصطلحات موضوعية: |
*TRANSFORMING growth factors-beta, *MICROPHYSIOLOGICAL systems, *PULMONARY fibrosis, *PROTEIN expression, *GENE expression |
| مستخلص: |
Introduction: Fibrotic cocktail (FC) is a combination of pro-fibrotic and pro-inflammatory mediators that induces early fibrotic changes in organotypic lung models. We hypothesised that transforming growth factor beta 1 (TGF-β1) alone induces a pro-fibrotic effect similar to FC. Our aim was to compare the pro-fibrotic effects of TGF-β1 with FC in human precision-cut lung slices (PCLS). Methods: PCLS from "healthy" lung tissue of cancer patients undergoing surgery (n = 7) were incubated with TGF-β1, FC or control for 72 h. Gene expression markers for myofibroblasts differentiation, extracellular matrix (ECM), as well as TGF-β receptors were assessed (RT-qPCR). ECM proteins expression in lysates and supernatant was assessed by ELISA and immunofluorescence. Results: We found that TGF-β1 significantly increased gene expression of ACTA2, COL1A1, CCN2, and VIM compared to control but also compared to FC. FC showed a significant increase of matrix metalloproteinase (MMP) 7 and 1 compared to control, while TGF-β receptor 2 was lower after FC compared to TGF-β1 or control. FC or TGF-β1 showed similar fibronectin protein expression in lysates and supernatants, while type I collagen protein expression in lysates was significantly greater with TGF-β1 compared to control. Conclusions: Our findings show that TGF-β1 induces consistent pro-fibrotic changes in PCLS after 72 h. Compared to TGF-β1, FC treatment resulted in reduced gene expression of TGF-β receptor 2 and increased MMPs expression, potentially mitigating the early pro-fibrotic effects. Selecting specific pro-fibrotic stimuli may be preferable depending on the research question and time point of interest in lung fibrosis studies using PCLS. [ABSTRACT FROM AUTHOR] |
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