Premium
Mitochondrial dysfunction in affected skin and increased mitochondrial DNA in serum from patients with psoriasis
Author(s) -
Therianou Anastasia,
Vasiadi Magdalini,
Delivanis Danae A.,
Petrakopoulou Theodora,
KatsarouKatsari Alexandra,
Antoniou Christina,
Stratigos Alexandros,
Tsilioni Irene,
Katsambas Andreas,
Rigopoulos Dimitris,
Theoharides Theoharis C.
Publication year - 2019
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13831
Subject(s) - psoriasis , mitochondrial dna , inflammation , apoptosis , keratinocyte , mitochondrion , biology , pathogenesis , real time polymerase chain reaction , calcineurin , microbiology and biotechnology , immunology , medicine , gene , biochemistry , cell culture , genetics , transplantation
Psoriasis is characterized by keratinocyte proliferation and chronic inflammation, but the pathogenesis is still unclear. Dysregulated mitochondria (mt) could lead to reduced apoptosis and extracellular secretion of mt DNA , acting as “innate pathogen” triggering inflammation. Serum was obtained from healthy volunteers and psoriatic patients. Mitochondrial DNA was extracted from the serum and amplified with quantitative PCR ( qPCR ). Punch biopsies were obtained from lesional and non‐lesional psoriatic skin (10 cm apart) and from healthy volunteers, were placed in RNA later and were stored at −80°C until RNA was extracted and cDNA was synthesized; gene expression of uncoupling protein 2 ( UCP 2), Dynamin‐related protein 1 (Drp1) and calcineurin, involved in the regulation of mitochondria function, was detected with qPCR . Mitochondrial DNA was significantly increased (7s, P = 0.0496 and Cytochrome B, CytB, P = 0.0403) in the serum of psoriatic patients (n = 63) as compared to controls (n = 27). Gene expression was significantly reduced for UCP 2 ( P = 0.0218), Drp1 ( P = 0.0001) and calcineurin ( P = 0.0001) in lesional psoriatic skin, as compared to non‐lesional or control skin. Increased serum extracellular mt DNA in psoriatic patients and decreased expression of mitochondrial regulatory proteins in psoriatic skin suggest increased inflammation and reduced keratinocyte apoptosis, respectively. Inhibitors of mt DNA secretion and/or UCP 2 stimulants may be potential treatment options.