Cargando…

Lysosome Alterations in the Human Epithelial Cell Line HaCaT and Skin Specimens: Relevance to Psoriasis

Despite the constantly updated knowledge regarding the alterations occurring in the cells of patients with psoriasis, the status and the role of the lysosome, a control center of cell metabolism, remain to be elucidated. The architecture of the epidermis is largely regulated by the action of lysosom...

Descripción completa

Detalles Bibliográficos
Autores principales: Bocheńska, Katarzyna, Moskot, Marta, Malinowska, Marcelina, Jakóbkiewicz-Banecka, Joanna, Szczerkowska-Dobosz, Aneta, Purzycka-Bohdan, Dorota, Pleńkowska, Joanna, Słomiński, Bartosz, Gabig-Cimińska, Magdalena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539968/
https://www.ncbi.nlm.nih.gov/pubmed/31067781
http://dx.doi.org/10.3390/ijms20092255
_version_ 1783422514818449408
author Bocheńska, Katarzyna
Moskot, Marta
Malinowska, Marcelina
Jakóbkiewicz-Banecka, Joanna
Szczerkowska-Dobosz, Aneta
Purzycka-Bohdan, Dorota
Pleńkowska, Joanna
Słomiński, Bartosz
Gabig-Cimińska, Magdalena
author_facet Bocheńska, Katarzyna
Moskot, Marta
Malinowska, Marcelina
Jakóbkiewicz-Banecka, Joanna
Szczerkowska-Dobosz, Aneta
Purzycka-Bohdan, Dorota
Pleńkowska, Joanna
Słomiński, Bartosz
Gabig-Cimińska, Magdalena
author_sort Bocheńska, Katarzyna
collection PubMed
description Despite the constantly updated knowledge regarding the alterations occurring in the cells of patients with psoriasis, the status and the role of the lysosome, a control center of cell metabolism, remain to be elucidated. The architecture of the epidermis is largely regulated by the action of lysosomes, possibly activating signaling pathways in the cellular crosstalk of keratinocytes—epidermal cells—with infiltrating immune cells. Thus, in the present study, lysosome alterations were examined in vitro and in situ using a two-dimensional (2D) keratinocyte model of HaCaT cells with “psoriasis-like” inflammation and skin specimens, respectively. Specific fluorescence and immunohistochemical staining showed an augmented level of acidic organelles in response to keratinocyte activation (mimicking a psoriatic condition while maintaining the membrane integrity of these structures) as compared with the control, similar to that seen in skin samples taken from patients. Interestingly, patients with the most pronounced PASI (Psoriasis Area and Severity Index), BSA (Body Surface Area), and DLQI (Dermatology Life Quality Index) scores suffered a high incidence of positive lysosomal-associated membrane protein 1 (LAMP1) expression. Moreover, it was found that the gene deregulation pattern was comparable in lesioned (PP) and non-lesioned (PN) patient-derived skin tissue, which may indicate that these alterations occur prior to the onset of the characteristic phenotype of the disease. Changes in the activity of genes encoding the microphthalmia family (MiT family) of transcription factors and mammalian target of rapamycin complex 1 (MTORC1) were also observed in the in vitro psoriasis model, indicating that the biogenesis pathway of this arm is inhibited. Interestingly, in contrast to the keratinocytes of HaCaT with “psoriasis-like” inflammation, LAMP1 was up-regulated in both PP and PN skin, which can be a potential sign of an alternative mechanism of lysosome formation. Defining the molecular profile of psoriasis in the context of “the awesome lysosome” is not only interesting, but also desired; therefore, it is believed that this paper will serve to encourage other researchers to conduct further studies on this subject.
format Online
Article
Text
id pubmed-6539968
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-65399682019-06-04 Lysosome Alterations in the Human Epithelial Cell Line HaCaT and Skin Specimens: Relevance to Psoriasis Bocheńska, Katarzyna Moskot, Marta Malinowska, Marcelina Jakóbkiewicz-Banecka, Joanna Szczerkowska-Dobosz, Aneta Purzycka-Bohdan, Dorota Pleńkowska, Joanna Słomiński, Bartosz Gabig-Cimińska, Magdalena Int J Mol Sci Article Despite the constantly updated knowledge regarding the alterations occurring in the cells of patients with psoriasis, the status and the role of the lysosome, a control center of cell metabolism, remain to be elucidated. The architecture of the epidermis is largely regulated by the action of lysosomes, possibly activating signaling pathways in the cellular crosstalk of keratinocytes—epidermal cells—with infiltrating immune cells. Thus, in the present study, lysosome alterations were examined in vitro and in situ using a two-dimensional (2D) keratinocyte model of HaCaT cells with “psoriasis-like” inflammation and skin specimens, respectively. Specific fluorescence and immunohistochemical staining showed an augmented level of acidic organelles in response to keratinocyte activation (mimicking a psoriatic condition while maintaining the membrane integrity of these structures) as compared with the control, similar to that seen in skin samples taken from patients. Interestingly, patients with the most pronounced PASI (Psoriasis Area and Severity Index), BSA (Body Surface Area), and DLQI (Dermatology Life Quality Index) scores suffered a high incidence of positive lysosomal-associated membrane protein 1 (LAMP1) expression. Moreover, it was found that the gene deregulation pattern was comparable in lesioned (PP) and non-lesioned (PN) patient-derived skin tissue, which may indicate that these alterations occur prior to the onset of the characteristic phenotype of the disease. Changes in the activity of genes encoding the microphthalmia family (MiT family) of transcription factors and mammalian target of rapamycin complex 1 (MTORC1) were also observed in the in vitro psoriasis model, indicating that the biogenesis pathway of this arm is inhibited. Interestingly, in contrast to the keratinocytes of HaCaT with “psoriasis-like” inflammation, LAMP1 was up-regulated in both PP and PN skin, which can be a potential sign of an alternative mechanism of lysosome formation. Defining the molecular profile of psoriasis in the context of “the awesome lysosome” is not only interesting, but also desired; therefore, it is believed that this paper will serve to encourage other researchers to conduct further studies on this subject. MDPI 2019-05-07 /pmc/articles/PMC6539968/ /pubmed/31067781 http://dx.doi.org/10.3390/ijms20092255 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bocheńska, Katarzyna
Moskot, Marta
Malinowska, Marcelina
Jakóbkiewicz-Banecka, Joanna
Szczerkowska-Dobosz, Aneta
Purzycka-Bohdan, Dorota
Pleńkowska, Joanna
Słomiński, Bartosz
Gabig-Cimińska, Magdalena
Lysosome Alterations in the Human Epithelial Cell Line HaCaT and Skin Specimens: Relevance to Psoriasis
title Lysosome Alterations in the Human Epithelial Cell Line HaCaT and Skin Specimens: Relevance to Psoriasis
title_full Lysosome Alterations in the Human Epithelial Cell Line HaCaT and Skin Specimens: Relevance to Psoriasis
title_fullStr Lysosome Alterations in the Human Epithelial Cell Line HaCaT and Skin Specimens: Relevance to Psoriasis
title_full_unstemmed Lysosome Alterations in the Human Epithelial Cell Line HaCaT and Skin Specimens: Relevance to Psoriasis
title_short Lysosome Alterations in the Human Epithelial Cell Line HaCaT and Skin Specimens: Relevance to Psoriasis
title_sort lysosome alterations in the human epithelial cell line hacat and skin specimens: relevance to psoriasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539968/
https://www.ncbi.nlm.nih.gov/pubmed/31067781
http://dx.doi.org/10.3390/ijms20092255
work_keys_str_mv AT bochenskakatarzyna lysosomealterationsinthehumanepithelialcelllinehacatandskinspecimensrelevancetopsoriasis
AT moskotmarta lysosomealterationsinthehumanepithelialcelllinehacatandskinspecimensrelevancetopsoriasis
AT malinowskamarcelina lysosomealterationsinthehumanepithelialcelllinehacatandskinspecimensrelevancetopsoriasis
AT jakobkiewiczbaneckajoanna lysosomealterationsinthehumanepithelialcelllinehacatandskinspecimensrelevancetopsoriasis
AT szczerkowskadoboszaneta lysosomealterationsinthehumanepithelialcelllinehacatandskinspecimensrelevancetopsoriasis
AT purzyckabohdandorota lysosomealterationsinthehumanepithelialcelllinehacatandskinspecimensrelevancetopsoriasis
AT plenkowskajoanna lysosomealterationsinthehumanepithelialcelllinehacatandskinspecimensrelevancetopsoriasis
AT słominskibartosz lysosomealterationsinthehumanepithelialcelllinehacatandskinspecimensrelevancetopsoriasis
AT gabigciminskamagdalena lysosomealterationsinthehumanepithelialcelllinehacatandskinspecimensrelevancetopsoriasis