DPP4 inhibitors increase differentially the expression of surfactant proteins in Fischer 344 rats

Schmiedl A, Gruetzner D, Hoffmann T, von Hörsten S, Stephan M (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Acta Physiologica Wiley-Blackwell

Publisher: Wiley-Blackwell

Book Volume: 212

Pages Range: 248-61

Journal Issue: 3

DOI: 10.1111/apha.12350

Abstract

Intact surface active agent (surfactant) composed of surfactant-associated proteins (SPs) and lipids is necessary for respiration and prevents alveoli from collapsing. CD26, a transmembrane glycoprotein exerting dipeptidyl peptidase activity (DPP4), highly expressed in lung parenchyma, is involved in inflammatory processes. A pharmacological inhibition of DPP4 influenced not only the inflammation but also elevated the SPs. Thus, DPP4 inhibitors may be a novel drug for treatment of diseases with surfactant deficiency. Therefore, we tested firstly the hypothesis that DPP4 inhibitors increase the expression of SPs in healthy rats.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.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.DPP4 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.

Authors with CRIS profile

Stephan von Hörsten Professur für Experimentelle Biomedizin

Involved external institutions

Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Probiodrug AG DE Germany (DE)

How to cite

APA:

Schmiedl, A., Gruetzner, D., Hoffmann, T., von Hörsten, S., & Stephan, M. (2014). DPP4 inhibitors increase differentially the expression of surfactant proteins in Fischer 344 rats. Acta Physiologica, 212(3), 248-61. https://doi.org/10.1111/apha.12350

MLA:

Schmiedl, A., et al. "DPP4 inhibitors increase differentially the expression of surfactant proteins in Fischer 344 rats." Acta Physiologica 212.3 (2014): 248-61.

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