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DPP 4 Inhibitors increase differentially the expression of surfactant proteins in Fischer 344 rats
Author(s) -
Schmiedl A.,
Grützner D.,
Hoffmann T.,
Hörsten S.,
Stephan M.
Publication year - 2014
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12350
Subject(s) - pulmonary surfactant , protein expression , chemistry , microbiology and biotechnology , pharmacology , biochemistry , biology , gene
Aim Intact surface active agent (surfactant) composed of surfactant‐associated proteins ( SP s) and lipids is necessary for respiration and prevents alveoli from collapsing. CD 26, a transmembrane glycoprotein exerting dipeptidyl peptidase activity ( DPP 4), highly expressed in lung parenchyma, is involved in inflammatory processes. A pharmacological inhibition of DPP 4 influenced not only the inflammation but also elevated the SP s. Thus, DPP 4 inhibitors may be a novel drug for treatment of diseases with surfactant deficiency. Therefore, we tested firstly the hypothesis that DPP 4 inhibitors increase the expression of SP s in healthy rats. Methods SP mRNA and protein expression were determined different times after nebulization of aerosolized DPP4 inhibitors [L‐isoleucine‐thiazolidide (L‐Ile‐Thia), L‐valine‐pyrrolidide (L‐Val‐Pyrr)], budesonide, saline or stereoisomers. Results Compared with negative controls (1) L‐Ile‐Thia as well as budesonide led to a significant higher and L‐Val‐Pyrr had the tendency to a significant higher expression of SP‐A mRNA 6 h after nebulization, (2) the expression of SP‐D mRNA increased significantly 6 h after nebulization with L‐Ile‐Thia and 3 and 6 h after nebulization with Val‐pyrr, (3) SP‐B mRNA levels showed significantly higher values 3 and 6 h after nebulization with L‐Val‐Pyrr, (4) protein levels of SP‐A, SP‐B and SP‐C were elevated significantly 6 h after nebulization with L‐Val‐Pyrr as well as with budesonide, and (5) phospholipids were also increased in response to DPP4 inhibition; the minimal surface tension was comparable. Conclusion DPP 4 inhibition influence differently the expression of surfactant proteins in healthy rats and may be suitable to elevate surfactant synthesis in different diseases accompanied with surfactant deficiencies.