Phenylbutyrate decreases type I collagen production in human lung fibroblasts

2004 ◽  
Vol 91 (4) ◽  
pp. 740-748 ◽  
Author(s):  
David C. Rishikof ◽  
Dennis A. Ricupero ◽  
Hanqiao Liu ◽  
Ronald H. Goldstein
Keyword(s):  
Type I Collagen ◽  
Human Lung ◽  
Lung Fibroblasts ◽  
Type I ◽  
Collagen Production ◽  
Human Lung Fibroblasts

Effect of subcellular matrix on glycosaminoglycan synthesis by human lung fibroblasts

1987 ◽  
Vol 63 (6) ◽  
pp. 2181-2188 ◽  
Author(s):  
D. J. Cui ◽  
B. A. Dubaybo ◽  
R. A. Durr ◽  
L. A. Thet
Keyword(s):  
Type I Collagen ◽  
Human Lung ◽  
Basement Membranes ◽  
Lung Fibroblasts ◽  
Type I ◽  
Glycosaminoglycan Synthesis ◽  
Human Lung Fibroblasts ◽  
Cell Matrix ◽  
Matrix Layer ◽  
The Matrix

The influences modulating glycosaminoglycan production by lung cells are not well understood. We examined the effect of three different subcellular matrices, plastic, type I collagen, and reconstituted basement membrane-like material (RBM), on the synthesis of sulfated glycosaminoglycans by cultured IMR-90 human lung fibroblasts. Accumulation of 35SO4-labeled glycosaminoglycans into the cell-matrix layer or medium was measured. Cells on collagen synthesized significantly less total glycosaminoglycans than cells on plastic but had a higher fraction of labeled glycosaminoglycans present in the cell-matrix layer (35 vs. 18%) with the increases being highest for dermatan and chondroitin sulfates. Cells grown on the RBM synthesized significantly more glycosaminoglycans than cells on plastic or collagen and also had 260% more labeled glycosaminoglycans present in the cell-matrix layer than cells on plastic. We conclude that the matrix to which lung fibroblasts are exposed can influence the amount and type of glycosaminoglycans synthesized and the degree of incorporation into the matrix. This may be relevant to fibrotic lungs with increased type I collagen or to severely injured lungs in which intra-alveolar fibroblasts are in contact with denuded basement membranes.

scholarly journals Hypoxia inhibits amino acid uptake in human lung fibroblasts

2000 ◽  
Vol 89 (4) ◽  
pp. 1425-1431 ◽  
Author(s):  
John L. Berk ◽  
Christine A. Hatch ◽  
Ronald H. Goldstein
Keyword(s):  
Amino Acid ◽  
Type I Collagen ◽  
Human Lung ◽  
Fold Increase ◽  
Amino Acid Uptake ◽  
Lung Fibroblasts ◽  
Substrate Affinity ◽  
Type I ◽  
Acid Uptake ◽  
Human Lung Fibroblasts

Hypoxia and amino acid deprivation downregulate expression of extracellular matrix genes in lung fibroblasts. We examined the effect of hypoxia on amino acid uptake and protein formation in human lung fibroblasts. Low O2 tension (0% O2) suppressed incorporation of [3H]proline into type I collagen without affecting [35S]methionine labeling of other proteins. Initial decreases in intracellular [3H]proline incorporation occurred after 2 h of exposure to 0% O2, with maximal suppression of intracellular [3H]proline levels at 6 h of treatment. Hypoxia significantly inhibited the uptake of radiolabeled proline, 2-aminoisobutyric acid (AIB), and 2-(methylamino)isobutyric acid (methyl-AIB) while inducing minor decreases in leucine transport. Neither cycloheximide nor indomethacin abrogated hypoxia-related suppression of methyl-AIB uptake. Efflux studies demonstrated that hypoxia inhibited methyl-AIB transport in a bidirectional fashion. The downregulation of amino acid transport was not due to a toxic effect; function recovered on return to standard O2 conditions. Kinetic analysis of AIB transport revealed a 10-fold increase in K maccompanied by a small increase in maximal transport velocity among cells exposed to 0% O2. These data indicate that low O2 tension regulates the system A transporter by decreasing transporter substrate affinity.

Olodaterol Inhibits Type I Collagen Synthesis By Human Lung Fibroblasts

2012 ◽  
Author(s):  
Xingqi Wang ◽  
Amy Nelson ◽  
Yoko Gunji ◽  
Maha Farid ◽  
Hesham Basma ◽  
...  
Keyword(s):  
Collagen Synthesis ◽  
Type I Collagen ◽  
Human Lung ◽  
Lung Fibroblasts ◽  
Type I ◽  
Human Lung Fibroblasts

scholarly journals Identification of TGF-β receptor-1 as a key regulator of carbon nanotube-induced fibrogenesis

2015 ◽  
Vol 309 (8) ◽  
pp. L821-L833 ◽  
Author(s):  
Anurag Mishra ◽  
Todd A. Stueckle ◽  
Robert R. Mercer ◽  
Raymond Derk ◽  
Yon Rojanasakul ◽  
...  
Keyword(s):  
Lung Fibrosis ◽  
Human Lung ◽  
Lung Fibroblasts ◽  
Screening Tests ◽  
Rapid Screening ◽  
Interstitial Tissue ◽  
Collagen Production ◽  
Human Lung Fibroblasts ◽  
Β Receptor ◽  
Tgf Β1

Carbon nanotubes (CNTs) induce rapid interstitial lung fibrosis, but the underlying mechanisms are unclear. Previous studies indicated that the ability of CNTs to penetrate lung epithelium, enter interstitial tissue, and stimulate fibroblasts to produce collagen matrix is important to lung fibrosis. In this study, we investigated the activation of transforming growth factor-β receptor-1 [TGF-β R1; i.e., activin receptor-like kinase 5 (ALK5) receptor] and TGF-β/Smad signaling pathway in CNT-induced collagen production in human lung fibroblasts. Human lung fibroblasts and epithelial cells were exposed to low, physiologically relevant concentrations (0.02–0.6 μg/cm2) of single-walled CNTs (SWCNT) and multiwalled CNTs (MWCNT) in culture and analyzed for collagen, TGF-β1, TGF-β R1, and SMAD proteins by Western blotting and immunofluorescence. Chemical inhibition of ALK5 and short-hairpin (sh) RNA targeting of TGF-β R1 and Smad2 were used to probe the fibrogenic mechanism of CNTs. Both SWCNT and MWCNT induced an overexpression of TGF-β1, TGF-β R1 and Smad2/3 proteins in lung fibroblasts compared with vehicle or ultrafine carbon black-exposed controls. SWCNT- and MWCNT-induced collagen production was blocked by ALK5 inhibitor or shRNA knockdown of TGF-β R1 and Smad2. Our results indicate the critical role of TGF-β R1/Smad2/3 signaling in CNT-induced fibrogenesis by upregulating collagen production in lung fibroblasts. This novel finding may aid in the design of mechanism-based risk assessment and development of rapid screening tests for nanomaterial fibrogenicity.

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