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Influence of the interaction between Ac‑SDKP and Ang II on the pathogenesis and development of silicotic fibrosis
- Source :
- Molecular Medicine Reports
- Publication Year :
- 2017
-
Abstract
- N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a natural tetrapeptide that is released from thymosin β4 by prolyl oligopeptides. It is hydrolyzed by the key enzyme of the renin-angiotensin system, angiotensin-converting enzyme (ACE). The aim of the present study was to investigate the alterations in Ac-SDKP and the ACE/angiotensin II (Ang II)/angiotensin II type 1 (AT1) receptor axis and its impact on the pathogenesis and development of silicotic fibrosis. For in vivo studies, a HOPE MED 8050 exposure control apparatus was used to establish different stages of silicosis in a rat model treated with Ac-SDKP. For in vitro studies, cultured primary lung fibroblasts were induced to differentiate into myofibroblasts by Ang II, and were pretreated with Ac-SDKP and valsartan. The results of the present study revealed that, during silicosis development, ACE/Ang II/AT1 expression in local lung tissues increased, whereas that of Ac-SDKP decreased. Ac-SDKP and the ACE/AT1/Ang II axis were inversely altered in the development of silicotic fibrosis. Ac-SDKP treatment had an anti-fibrotic effect in vivo. Compared with the silicosis group, the expression of α-smooth muscle actin (α-SMA), Collagen (Col) I, Fibronectin (Fn) and AT1 were significantly downregulated, whereas matrix metalloproteinase-1 (MMP-1) expression and the MMP-1/tissue inhibitor of metalloproteinases-1 (TIMP-1) ratio was increased in the Ac-SDKP treatment group. In vitro, pre-treatment with Ac-SDKP or valsartan attenuated the expression of α-SMA, Col I, Fn and AT1 in Ang II-induced fibroblasts. In addition, MMP-1 expression and the MMP-1/TIMP-1 ratio were significantly higher in Ac-SDKP and valsartan pre-treatment groups compared with the Ang II group. In conclusion, the results of the present study suggest that an imbalance between Ac-SDKP and ACE/Ang II/AT1 molecules promotes the development of silicosis and that Ac-SDKP protects against silicotic fibrosis by inhibiting Ang II-induced myofibroblast differentiation and extracellular matrix production.
- Subjects :
- 0301 basic medicine
Male
Cancer Research
medicine.medical_specialty
Silicosis
renin-angiotensin system
Peptidyl-Dipeptidase A
Biochemistry
Collagen Type I
Receptor, Angiotensin, Type 1
03 medical and health sciences
Fibrosis
In vivo
N-acetyl-seryl-aspartyl-lysyl-proline
Internal medicine
Renin–angiotensin system
Genetics
medicine
Animals
Myofibroblasts
Molecular Biology
Lung
Angiotensin II receptor type 1
Tissue Inhibitor of Metalloproteinase-1
biology
Chemistry
Angiotensin II
Articles
medicine.disease
myofibroblast
Rats
Fibronectin
030104 developmental biology
Endocrinology
Oncology
Valsartan
biology.protein
Molecular Medicine
Matrix Metalloproteinase 1
Myofibroblast
Oligopeptides
hormones, hormone substitutes, and hormone antagonists
Biomarkers
medicine.drug
Protein Binding
Subjects
Details
- ISSN :
- 17913004
- Volume :
- 17
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Molecular medicine reports
- Accession number :
- edsair.doi.dedup.....b1a8910308c5878fa6c2f258d7ebb5e2