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Apoptosis

, Volume 24, Issue 1–2, pp 95–107 | Cite as

Klotho modulates ER-mediated signaling crosstalk between prosurvival autophagy and apoptotic cell death during LPS challenge

  • Jennifer MytychEmail author
  • Przemyslaw Solek
  • Marek Koziorowski
Article

Abstract

Bacterial endotoxins have been shown to induce prosurvival autophagy or apoptosis in fibroblasts and thus impair the wound healing process. Endoplasmic reticulum has been proposed as a molecular switch between these processes and klotho protein possessing pleiotropic characteristics seems to be involved in both processes, however the exact molecular mechanism is unknown. In this study, we have evaluated the effect of klotho silencing on human fibroblasts exposed to a non-toxic dose of lipopolysaccharide in terms of in vitro wound healing ability. We show for the first time, that klotho silencing in fibroblasts intensified lipopolysaccharide-induced oxidative stress and inflammatory response, what resulted in genomic instability, p-eIF2a-mediated ER stress, retardation of prosurvival autophagy, induction of apoptotic cell death and finally in impaired wound closure. Therefore, our data suggest that klotho serves as a part of cellular defense mechanism engaged in providing protection against bacterial infections during wound healing by modulating ER-signaling crosstalk between autophagy and apoptosis.

Keywords

Klotho Fibroblasts ER stress Autophagy LPS 

Notes

Acknowledgements

The authors would like to thank Slawomir Nowak, MSc for providing antibodies against HMOX-1 and HMOX-2.

Author contributions

JM: performed the experiments, analyzed the data, carried out data interpretation, wrote the paper, conceived and designed the experiments; PS: performed the experiments, analyzed the data, carried out data interpretation; MK: conceived and designed the experiments; carried out data interpretation.

Compliance with ethical standards

Conflict of interest

The authors declare no competing interests.

Supplementary material

10495_2018_1496_MOESM1_ESM.docx (13 kb)
Supplementary material 1 (DOCX 12 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Jennifer Mytych
    • 1
    • 2
    Email author
  • Przemyslaw Solek
    • 1
    • 2
  • Marek Koziorowski
    • 1
    • 2
  1. 1.Department of Animal Physiology and Reproduction, Faculty of BiotechnologyUniversity of RzeszowKolbuszowaPoland
  2. 2.Centre of Applied Biotechnology and Basic SciencesUniversity of RzeszowKolbuszowaPoland

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