Lysosome alterations in the human epithelial cell line HaCaT and skin specimens: relevance to psoriasis
Katarzyna Bocheńska , Marta Moskot , Marcelina Malinowska , Joanna Jakóbkiewicz-Banecka , Aneta Szczerkowska-Dobosz , Dorota Purzycka-Bohdan , Joanna Pleńkowska , Bartosz Słomiński , Magdalena Gabig-Cimińska
AbstractDespite 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.
|Journal series||International Journal of Molecular Sciences, ISSN 1422-0067, (N/A 100 pkt)|
|Publication size in sheets||1.1|
|Keywords in English||skin disorder, psoriasis, in vitro and in situ studies, human cell line and skin specimens, lysosomal compartments|
|ASJC Classification||; ; ; ; ; ; ;|
|License||Journal (articles only); published final; ; with publication|
|Score||= 100.0, 10-01-2020, ArticleFromJournal|
|Publication indicators||= 0; : 2018 = 1.224; : 2018 = 4.183 (2) - 2018=4.331 (5)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.