Psoriatic skin transcript phenotype: androgen/estrogen and cortisone/cortisol imbalance with increasing DNA damage response
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View abstract on PubMed
Summary
This summary is machine-generated.Psoriasis disrupts skin barrier and immune defenses, linked to DNA damage repair (DDR). This study reveals altered steroid hormone pathways and androgen dominance in psoriatic skin, suggesting new therapeutic targets for this chronic skin condition.
Area Of Science
- Dermatology
- Genetics
- Endocrinology
Background
- Psoriasis involves epidermal barrier dysfunction, keratinocyte abnormalities, and inflammation.
- Genotoxicity, indicated by short telomeres, suggests compromised immune defenses and DNA damage repair (DDR) in psoriasis patients.
- Crosstalk between DDR machinery and hormonal signaling pathways influences disease progression and treatment response.
Purpose Of The Study
- To investigate parallel alterations in steroid biosynthesis and genomic stability markers during psoriatic skin development.
- To understand the interplay between the steroid pathway and DNA damage response in psoriasis pathogenesis.
Main Methods
- Analysis of skin (lesional and non-lesional) and blood samples from psoriasis patients and healthy controls.
- Real-Time-PCR to quantify transcript levels of estrogen receptors (ESR1, ESR2), androgen receptor (AR), glucocorticoid/mineralocorticoid receptors (NR3C1, NR3C2), steroidogenic enzymes (HSD11B1/HSD11B2), and DNA damage sensors.
Main Results
- Significant decrease in ESR1, ESR2, HSD11B1, NR3C1, NR3C2, POLH, and SMC1A transcripts in lesional psoriatic skin compared to controls.
- Dramatic increase in AR, TREX1, RAD1, and SSBP3 transcripts in lesional psoriatic skin.
- Disruption of steroidogenic pathway regulation observed in lesional psoriatic tissue.
Conclusions
- Psoriatic lesional tissue exhibits disrupted steroidogenic pathway regulation, with insufficient glucocorticoid/mineralocorticoid response and an altered estrogen/androgen balance favoring androgens.
- Increased androgen response combined with DDR may elevate psoriasis risk.
- Findings suggest potential for novel therapeutic strategies targeting the interaction between steroidogenesis and DNA damage response in psoriasis.
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