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Co-expression of the homologous proteases fibroblast activation protein and dipeptidyl peptidase-IV in the adult human Langerhans islets

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Abstract

Fibroblast activation protein (FAP, seprase, EC 3.4.21.B28) and dipeptidyl peptidase-IV (DPP-IV, CD26, EC 3.4.14.5) are homologous serine proteases implicated in the modulation of the bioavailability and thus the function of a number of biologically active peptides. In spite of their generally nonoverlapping expression patterns, DPP-IV and FAP are co-expressed and probably co-regulated in certain cell types suggesting that for some biological processes their functional synergy is essential. By an in situ enzymatic activity assay, we show an abundant DPP-IV-like enzymatic activity sensitive to a highly specific DPP-IV inhibitor sitagliptin and corresponding DPP-IV immunoreactivity in the adult human islets of Langerhans. Moreover, the homologous protease FAP was present in the human endocrine pancreas and was co-expressed with DPP-IV. DPP-IV and FAP were found in the pancreatic alpha cells as determined by the co-localization with glucagon immunoreactivity. In summary, we show abundant enzymatic activity of the canonical DPP-IV (CD26) in Langerhans islets in the natural tissue context and demonstrate for the first time the co-expression of FAP and DPP-IV in pancreatic alpha cells in adult humans. Given their ability to proteolytically modify several biologically active peptides, both proteases have the potential to modulate the paracrine signaling in the human Langerhans islets.

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Acknowledgments

This work was supported by the grants of the Internal Grant Agency of the Ministry of Health of the Czech Republic IGA NT 14254-3/2013, PRVOUK-P27/LF1/1 and UNCE 204013.

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Laboratory of Cancer Cell Biology, Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, U Nemocnice 5, 128 53, Prague 2, Czech Republic

    Petr Busek & Aleksi Sedo

  2. Department of Pathology, Military University Hospital Prague, Prague 6, Czech Republic

    Petr Hrabal

  3. Department of Medicine, First Faculty of Medicine, Charles University in Prague and Military University Hospital Prague, Prague 6, Czech Republic

    Premysl Fric

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  1. Petr Busek
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  2. Petr Hrabal
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  3. Premysl Fric
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Correspondence to Petr Busek or Aleksi Sedo.

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Busek, P., Hrabal, P., Fric, P. et al. Co-expression of the homologous proteases fibroblast activation protein and dipeptidyl peptidase-IV in the adult human Langerhans islets. Histochem Cell Biol 143, 497–504 (2015). https://doi.org/10.1007/s00418-014-1292-0

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