Anti-fibrotic role of AcSDKP through inhibition of P38MAPK pathway activity mediated transforming growth beta receptors in rat with silicosis / 中华劳动卫生职业病杂志
Chinese Journal of Industrial Hygiene and Occupational Diseases
; (12): 340-347, 2014.
Article
in Zh
| WPRIM
| ID: wpr-306304
Responsible library:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the distribution and expression of transforming growth factor beta (TGF-β) receptors I and II, p38 mitogen-activated protein kinase (p38 MAPK), and type I and type III collagen in the lungs of rats with silicosis and cultured pulmonary fibroblasts, and to investigate the relationship of the anti-fibrosis effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) with its inhibition of TGF-β receptor-mediated p38 MAPK pathway activity.</p><p><b>METHODS</b>Rats were randomly divided into control group, silicosis model group, and AcSDKP treatment group (n = 10 for each group). For the model group and AcSDKP treatment group, rats were intratracheally instilled with silica to establish a silicosis model. Cultured pulmonary fibroblasts from neonatal rats were divided into control group, TGF-β1 stimulation group, TGF-β receptor inhibition group, p38 MAPK pathway inhibition group, and AcSDKP treatment group. The protein expression of TGF-β receptors I and II, p38 MAPK, and type I and type III collagen were determined by immunohistochemistry and Western blot. The mRNA expression of TGF-β receptors I and II were determined by real-time PCR. The distribution and nuclear translocation of phospho-p38 MAPK in cultured fibroblasts were determined by laser scanner confocal microscopy.</p><p><b>RESULTS</b>In the AcSDKP treatment group, AcSDKP reduced the expression of TGF-β receptors I and II, phospho-p38 MAPK, and type I and type III collagen to 86.12%, 41.01%, 42.63%, 89.05%, and 52.71%, respectively, of those of the silicosis model group (P < 0.05). In cultured fibroblasts, AcSDKP reduced the mRNA expression of TGF-β receptors I and II to 42.26% and 54.33%, respectively, of those of the TGF-β1 stimulation group; the protein expression of TGF-β receptors I and II, phospho-p38 MAPK, and type 1 and type III collagen was reduced to 58.14%, 51.40%, 45.6%, 58.04%, and 44.74%, respectively, of those of the TGF-β1 stimulation group. The phospho-p38 MAPK translocation from plasma to the nucleus was also inhibited; the nucleus/plasma ratio of p38 MAPK and the protein expression of type I and type III collagen were reduced to 68.60%, 58.04%, and 44.74%, respectively, of those of the TGF-β stimulation group (P < 0.05).</p><p><b>CONCLUSION</b>AcSDKP can inhibit the expression of collagen through inhibition of TGF-β receptor-mediated p38 MAPK pathway activity, and is thus able to exert anti-fibrosis effect in rats with silicosis.</p>
Full text:
1
Database:
WPRIM
Main subject:
Oligopeptides
/
Pharmacology
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Silicosis
/
Cells, Cultured
/
Transforming Growth Factor beta
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Collagen
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Rats, Wistar
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Protein Serine-Threonine Kinases
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Receptors, Transforming Growth Factor beta
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MAP Kinase Signaling System
Type of study:
Prognostic_studies
Limits:
Animals
Language:
Zh
Journal:
Chinese Journal of Industrial Hygiene and Occupational Diseases
Year:
2014
Document type:
Article