Enalapril stimulates collagen biosynthesis through prolidase-dependent mechanism in cultured fibroblasts
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- 作者：Lukasz Szoka ; Ewa Karna ; Renata Pawlak Morka…
- 关键词：Enalapril ; Enalaprilat ; Collagen biosynthesis ; Fibroblasts ; Prolidase
- 刊名：Naunyn-Schmiedeberg's Archives of Pharmacology
- 出版年：2015
- 出版时间：June 2015
- 年：2015
- 卷：388
- 期：6
- 页码：677-683
- 全文大小：539 KB
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Kouba DJ, Chung KY, Nishiyama T, Vindevoghel L, Kon A, Klement J - 作者单位：Lukasz Szoka (1)
Ewa Karna (1)
Renata Pawlak Morka (1)
Jerzy A. Palka (1)
1. Department of Medicinal Chemistry, Medical University in Bialystok, Mickiewicza 2 D, 15-222, Bialystok, Poland - 刊物类别：Biomedical and Life Sciences
- 刊物主题：Biomedicine
Pharmacology and Toxicology
Neurosciences - 出版者：Springer Berlin / Heidelberg
- ISSN：1432-1912
文摘
The mechanism of a lower incidence of dermatological manifestations in patients treated with enalapril compared to patients treated with other ACE-inhibitors, e.g., captopril, is not known. The finding that prolidase plays an important role in collagen biosynthesis and that some angiotensin-converting enzyme inhibitors affect prolidase activity led us to evaluate its effect on collagen biosynthesis in cultured human skin fibroblasts. Since insulin-like growth factor (IGF-I) and transforming growth factor beta 1 (TGF-β1) are the most potent stimulators of both collagen biosynthesis and prolidase activity, and prolidase is regulated by β1 integrin signaling, the effect of enalapril and enalaprilat on IGF-IR, TGF-β1, and β1 integrin receptor expressions was evaluated. Cells were treated with milimolar concentrations (0.3 and 0.5?mM) of enalapril and enalaprilat for 24?h. The activity of prolidase was determined by colorimetic assay. Collagen biosynthesis was evaluated by radiometric assay. Expression of signaling proteins was evaluated using Western blot. It was found that enalapril- and enalaprilat-dependent increase in prolidase activity and expression was accompanied by parallel increase in collagen biosynthesis. The exposure of the cells to 0.5?mM enalapril and enalaprilat contributed to increase in IGF-IR and α2β1 integrin receptor as well as TGF-β1 and NF-κB p65 expressions. Enalapril- and enalaprilat-dependent increase of collagen biosynthesis in fibroblasts results from increase of prolidase activity and expression, which may undergo through activation of α2β1 integrin and IGF-IR signaling as well as upregulation of TGF-β1 and NF-κB p65, the inhibitor of collagen gene expression.