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RESEARCH PAPER
Cathelicidin influence on pathological activation of Wnt pathway in murine model of hypersensitivity pneumonitis
1
Department of Medical Biology, Institute of Rural Health, Lublin, Poland
2
Digital Global Health Working Group, Institute of Global Health, University Hospital, Heidelberg, Germany
3
Department of Biological Health Hazards and Parasitology, Institute of Rural Health, Lublin, Poland
4
Department of Pneumonology, Oncology and Allergology, Medical University, Lublin, Poland
Corresponding author
Marta Kinga Lemieszek
Department of Medical Biology, Institute of Rural Health, Lublin, Poland, Poland
Department of Medical Biology, Institute of Rural Health, Lublin, Poland, Poland
Ann Agric Environ Med. 2022;29(3):358-364
KEYWORDS
extrinsic allergic alveolitisPantoea agglomeranslung fibrosisdefence peptidesimmune peptidesWnt/ β-Catenin pathway
TOPICS
ABSTRACT
Introduction and objective:
Cathelicidin (CRAMP) is a defence peptide with a wide range of biological responses including antimicrobial, immunomodulatory and wound healing. Furthermore, our previous studies suggested the possibility of using cathelicidin in the prevention and treatment of pulmonary fibrosis in the course of hypersensitivity pneumonitis (HP). The molecular mechanism of CRAMP action, however, was not fully explained. Due to the fact that several studies indicated the Wnt signals pathways as a key player in wound healing and fibrosis, studies focused on this pathway in order to explain the above-mentioned therapeutic potential of cathelicidin in HP development.
Material and methods:
The study was conducted in a murine model of HP, wherein lung fibrosis is induced in mice strain C57BL/6J by chronic exposure to saline extract of P. agglomerans (SE-PA). Cathelicidin was administered in the an form of aerosol during HP development. Changes in the expression of genes and proteins involved in signals transduction in the Wnt/β-Catenin pathway were examined in lung tissue homogenates by RealTime PCR and Western Blotting, respectively.
Results:
The study revealed that cathelicidin decreased the elevated level of components of the Wnt/β-Catenin pathway (Ctnnd1/β-Catenin, Wnt1/WNt1, Wnt3a/Wnt3a, Wnt5a/Wnt5a) in the murine model of HP. Furthermore, CRAMP administered together with SE-PA inhibited the transcription function of β-catenin, leading to a decrease in abnormal expression of profibrotic molecules: Cyclin D1, c-Myc, MMP-7. Nevertheless, cathelicidin was not able to completely neutralize the negative changes induced by SE-PA.
Conclusions:
The study demonstrated the beneficial effect of exogenous cathelicidin on signals transduction in the Wnt/β-Catenin pathway, which may prevent fibrosis development in HP.
Cathelicidin (CRAMP) is a defence peptide with a wide range of biological responses including antimicrobial, immunomodulatory and wound healing. Furthermore, our previous studies suggested the possibility of using cathelicidin in the prevention and treatment of pulmonary fibrosis in the course of hypersensitivity pneumonitis (HP). The molecular mechanism of CRAMP action, however, was not fully explained. Due to the fact that several studies indicated the Wnt signals pathways as a key player in wound healing and fibrosis, studies focused on this pathway in order to explain the above-mentioned therapeutic potential of cathelicidin in HP development.
Material and methods:
The study was conducted in a murine model of HP, wherein lung fibrosis is induced in mice strain C57BL/6J by chronic exposure to saline extract of P. agglomerans (SE-PA). Cathelicidin was administered in the an form of aerosol during HP development. Changes in the expression of genes and proteins involved in signals transduction in the Wnt/β-Catenin pathway were examined in lung tissue homogenates by RealTime PCR and Western Blotting, respectively.
Results:
The study revealed that cathelicidin decreased the elevated level of components of the Wnt/β-Catenin pathway (Ctnnd1/β-Catenin, Wnt1/WNt1, Wnt3a/Wnt3a, Wnt5a/Wnt5a) in the murine model of HP. Furthermore, CRAMP administered together with SE-PA inhibited the transcription function of β-catenin, leading to a decrease in abnormal expression of profibrotic molecules: Cyclin D1, c-Myc, MMP-7. Nevertheless, cathelicidin was not able to completely neutralize the negative changes induced by SE-PA.
Conclusions:
The study demonstrated the beneficial effect of exogenous cathelicidin on signals transduction in the Wnt/β-Catenin pathway, which may prevent fibrosis development in HP.
ACKNOWLEDGEMENTS
The studies were supported by the National Science Centre, Poland [Grant No, 2015/19/D/NZ7/02952, 2016].
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