Transforming Growth Factor-β1-Induced Activation of the Raf-MEK-MAPK Signaling Pathway in Rat Lung Fibroblasts via a PKC-Dependent Mechanism

1998 ◽  
Vol 249 (2) ◽  
pp. 456-460 ◽  
Author(s):  
Andreas Axmann ◽  
Dagmar Seidel ◽  
Thomas Reimann ◽  
Ute Hempel ◽  
Klaus-Wolfgang Wenzel
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Lung Fibroblasts ◽  
Rat Lung ◽  
Dependent Mechanism

Glucocorticoid-induced down regulation of transforming growth factor-β1 in adult rat lung fibroblasts

Lung ◽  
1995 ◽  
Vol 173 (2) ◽  
pp. 71-78 ◽  
Author(s):  
S. Shull ◽  
N. Meisler ◽  
M. Absher ◽  
S. Phan ◽  
K. Cutroneo
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Lung Fibroblasts ◽  
Rat Lung ◽  
Down Regulation ◽  
Adult Rat

scholarly journals Regulation of Cellular Senescence Is Independent from Profibrotic Fibroblast-Deposited ECM

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1628
Author(s):  
Kaj E. C. Blokland ◽  
Habibie Habibie ◽  
Theo Borghuis ◽  
Greta J. Teitsma ◽  
Michael Schuliga ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cellular Senescence ◽  
Transforming Growth Factor ◽  
Cell Function ◽  
Smooth Muscle Actin ◽  
Transforming Growth Factor Β1 ◽  
Tissue Growth ◽  
Alveolar Epithelial Cells ◽  
Lung Fibroblasts ◽  
Alpha Smooth Muscle Actin

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with poor survival. Age is a major risk factor, and both alveolar epithelial cells and lung fibroblasts in this disease exhibit features of cellular senescence, a hallmark of ageing. Accumulation of fibrotic extracellular matrix (ECM) is a core feature of IPF and is likely to affect cell function. We hypothesize that aberrant ECM deposition augments fibroblast senescence, creating a perpetuating cycle favouring disease progression. In this study, primary lung fibroblasts were cultured on control and IPF-derived ECM from fibroblasts pretreated with or without profibrotic and prosenescent stimuli, and markers of senescence, fibrosis-associated gene expression and secretion of cytokines were measured. Untreated ECM derived from control or IPF fibroblasts had no effect on the main marker of senescence p16Ink4a and p21Waf1/Cip1. However, the expression of alpha smooth muscle actin (ACTA2) and proteoglycan decorin (DCN) increased in response to IPF-derived ECM. Production of the proinflammatory cytokines C-X-C Motif Chemokine Ligand 8 (CXCL8) by lung fibroblasts was upregulated in response to senescent and profibrotic-derived ECM. Finally, the profibrotic cytokines transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF) were upregulated in response to both senescent- and profibrotic-derived ECM. In summary, ECM deposited by IPF fibroblasts does not induce cellular senescence, while there is upregulation of proinflammatory and profibrotic cytokines and differentiation into a myofibroblast phenotype in response to senescent- and profibrotic-derived ECM, which may contribute to progression of fibrosis in IPF.

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