Psoriatic skin transcript phenotype: androgen/estrogen and cortisone/ cortisol imbalance with increasing DNA damage response
Yükleniyor...
Tarih
2024
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Springer Science and Business Media B.V.
Erişim Hakkı
info:eu-repo/semantics/embargoedAccess
Özet
Patients prone to psoriasis suffer after a breakdown of the epidermal barrier and developpoorly healing lesions with abnormal proliferation of keratinocytes. Strong inflammatory reactions withgenotoxicity (short telomeres) suggest impaired immune defenses with DNA damage repair response(DDR) in patients with psoriasis. Recent evidence indicates the existence of crosstalk mechanismslinking the DDR machinery and hormonal signaling pathways that cooperate to influence bothprogressions of many diseases and responses to treatment. The aim of this study was to clarify whethersteroid biosynthesis and genomic stability markers are altered in parallel during the formation ofpsoriatic skin. Understanding the interaction of the steroid pathway and DNA damage response iscrucial to addressing underlying fundamental issues and managing resulting epidermal barrierdisruption in psoriasis. Methods: Skin (Lesional, non-lesional) and blood samples from twenty psoriasis patients and fifteen healthy volunteers were collected. Real-Time-PCR study was performed to assess levels of known transcripts such as: estrogen (ESR1, ESR2), androgen (AR), glucocorticoid/mineralocorticoid receptors (NR3C1, NR3C2), HSD11B1/HSD11B2, and DNA damage sensors (SMC1A, TREX1, TREX2, SSBP3, RAD1, RAD18, EXO1, POLH, HUS1). Results: We found that ESR1, ESR2, HSD11B1, NR3C1, NR3C2, POLH, and SMC1A transcripts were significantly decreased and AR, TREX1, RAD1, and SSBP3 transcripts were increased dramatically in the lesional skin compared to skin samples of controls. Conclusion: We found that the regulation of the steroidogenic pathway was disrupted in the lesional tissue of psoriasis patients and that a sufficient glucocorticoid and mineralocorticoid response did not form and the estrogen/androgen balance was altered in favour of androgens. We suggest that an increased androgen response in the presence of DDR increases the risk of developing psoriasis. Although this situation may be the cause or the consequence of a disruption of the epidermal barrier, our data suggest developing new therapeutic strategies.
Açıklama
Anahtar Kelimeler
Genome Integrity, Psoriasis, Steroidogenic Pathway, Transcript Profiles
Kaynak
Molecular Biology Reports
WoS Q Değeri
N/A
Scopus Q Değeri
Q2
Cilt
51
Sayı
1
