Peptide derived from progranulin of the carcinogenic liver fluke, Opisthorchis viverrini stimulates cell hyperproliferation and proinflammatory cytokine production.

Autor:	Hembasat T; Khon Kaen University Faculty of Medicine., Chaiyadet S; Khon Kaen University Faculty of Medicine., Ittiprasert W; GWU: George Washington University., Smout MJ; James Cook University - Cairns Campus., Young ND; The University of Melbourne., Loukas A; James Cook University - Cairns Campus., Brindley PJ; GWU: George Washington University., Laha T; Khon Kaen University Faculty of Medicine.
Jazyk:	angličtina
Zdroj:	Research square [Res Sq] 2023 Mar 14. Date of Electronic Publication: 2023 Mar 14.
DOI:	10.21203/rs.3.rs-2586058/v1
Abstrakt:	Purpose: Progranulin (PGRN) is a secreted glycoprotein growth factor with roles in wound healing, inflammation, angiogenesis and malignancy. An orthologue of the gene encoding human PGRN was identified in the carcinogenic liver fluke Opisthorchis viverrini . Methods: Sequence structure, general characteristics and possible function of O. viverrini PGRN was analyzed using bioinformatics. Expression profiles were investigated with quantitative RT-PCR, western blot and immunolocalization. A specific peptide of Ov -PGRN was used to investigate a role for this molecule in pathogenesis. Results: The structure of the gene coding for O. viverrini PGRN was 36,463 bp in length, and comprised of 13 exons, 12 introns, and a promoter sequence. The Ov-pgrn mRNA is 2,768 bp in length and encodes an 846 amino acids with a predicted molecular mass of 91.61 kDa. Ov -PGRN exhibited one half and seven complete granulin domains. Phylogenetic analysis revealed that Ov -PGRN formed its closest relationship with PGRN of liver flukes in the Opisthorchiidae. Transcripts of Ov-pgrn were detected in several developmental stages, with highest expression in the metacercaria, indicating that Ov -PGRN may participate as a growth factor in the early development of O. viverrini . Western blot analysis revealed the presence of detected Ov -PGRN in both soluble somatic or excretory/secretory products, and immunolocalization indicated high levels of expression in the tegument and parenchyma of the adult fluke. Co-culture of a human cholangiocyte cell line and a peptide fragment of Ov -PGRN stimulated proliferation of cholangiocytes and upregulation of expression of the cytokines IL6 and IL8. Conclusion: Ov-PGRN is expressed throughout the life cycle of liver fluke, and likely plays a key role in development and growth. Competing Interests: Conflict of interest – disclosure statement The authors declare no conflict of interest.
Databáze:	MEDLINE
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