Investigation of ADAMTS9 and ADAMTS15 mRNA Expression Levels in Psoriasis and Psoriatic Arthritis Patients

Öz

Background: In this study, we aimed to investigate the mRNA expression levels of ADAMTS9 and ADAMTS15 in peripheral blood mononuclear cells (PBMCs) of psoriasis (PsO) and psoriatic arthritis (PsA) patients and the effects of TNF-α/MAPK and IL-1β/NFkB signaling pathways on the regulation of the expression of these genes. Materials and Methods: 15 PsO and 15 PsA patients and 15 healthy individuals (control) were included in the study. After PBMCs were isolated from venous blood, ADAMTS9 and ADAMTS15 mRNA expression levels were measured by Real-Time Quantitative PCR (RT-qPCR). Results: It was found that ADAMTS9 mRNA expression in PBMCs did not change between groups, while the level of ADAMTS15 mRNA expression increased significantly in the PsA group compared to the control and PsO gro-ups. ADAMTS9 expression was observed not changed in the control and PsA groups in response to TNF-α stimula-tion, but decreased in the PsO group. However; TNF-α stimulation led to an increase in ADAMTS15 expression in the control group but did not change in the PsO and PsA groups. It has been revealed that the formation of TNF-α response and related changes in ADAMTS9 and ADAMTS15 expressions were regulated by MAP kinase genes (Erk1/2, p38 and JNK). ADAMTS9 expression was determined not affected by IL-1β stimulation, however; ADAMTS15 mRNA expression was decreased only in the PsA group. In addition, NFkB signaling molecule was involved in the formation of the IL-1β response and the regulation of ADAMTS15 expression. Conclusions: ADAMTS15 expression increased in PBMCs of PsA patients is regulated by the IL-1β/NFkB signaling pathway. An increase in ADAMTS15 mRNA expressin level may play a role in PsA pathogenesis. Furthermore, the expression level of ADAMTS15 has a potential to be used as an important biomarker in monitoring the risk of PsA development for PsO patients.

Anahtar Kelimeler

• ADAMTS9
• ADAMTS15
• Psoriasis
• Psoriatik Artrit

Proje Numarası

(TÜBİTAK) 214S024 (DÜBAP) Tıp.16.024

Psoriasis ve Psoriatik Artrit Hastalarında ADAMTS9 ve ADAMTS15 mRNA Ekspresyon Düzeylerinin Araştırılması

Öz

Amaç: Bu çalışmada, ADAMTS9 ve ADAMT15’ in psoriasis (PsO) ve psoriatik artrit (PsA) hastalarının periferik kan mononükleer hücrelerindeki (PBMC) mRNA ekspresyon düzeylerini ve bu genlerin ekspresyonlarının regülasyonunda TNF-α/MAPK ve IL-1β/NFkB sinyal yolaklarının etkilerini araştırmayı amaçladık. Materyal ve metod: 15 PsO ve 15 PsA hastaları ile 15 sağlıklı birey (kontrol) çalışmaya dahil edildi. PBMC hücreleri venöz kandan izole edildikten sonra, ADAMTS9 ve ADAMTS15 mRNA ekspresyon düzeyleri Eş Zamanlı-Kantitatif qPCR (RT-qPCR) ile ölçüldü. Bulgular: PBMC hücrelerinde ADAMTS9 mRNA ekspresyonunun gruplar arasında farklılık göstermediği, ADAMTS15 mRNA ekspresyon düzeyinin ise PsA grubunda kontrol ve PsO gruplarına oranla önemli bir artış gösterdiği bulunmştur. TNF-α stimülasyonu sonucu ADAMTS9 mRNA ekspresyonunun kontrol ve PsA gruplarında değişmediği, ancak PsO grubunda azalış gösterdiği gözlemlenmiştir. ADAMTS15 mRNA ekspresyonunun ise TNF-α stimülasyonu sonucu kontrol grubunda artış gösterdiği ancak PsO ve PsA gruplarında değişmediği saptanmıştır. TNF-α yanıtının oluşması ve buna bağlı ADAMTS9 ve ADAMTS15 mRNA ekpresyonundaki değişikliklerin MAP kinaz genleri (Erk1/2, p38 ve JNK) tarafından regüle edildiği ortaya konmuştur. IL-1β stimülasyonunun ADAMTS9 ekspresyonunda farklılık oluşturmadığı, ADAMTS15 mRNA ekspresyonunda ise sadece PsA grubunda azalmaya neden olduğu tespit edilmiştir. Ayrıca, IL-1β yanıtının oluşması ve ADAMTS15 ekspresyonun regülasyonunda NFkB sinyal molekünün etkili olduğu bulunmuştur. Sonuç: PsA hastalarının PBMC hücrelerinde artış gösteren ADAMTS15 mRNA ekresyonu IL-1β/NFkB sinyal yolağı tarafından regüle edilmektedir. ADAMTS15 mRNA ekspresyon düzeyindeki artış PsA patogenezinde rol oynayabilir. Ayrıca, ADAMS15 mRNA ekspresyon düzeyinin PsO hastaları için PsA gelişim riskinin takibinde önemli bir biyobelirteç olarak kullanılabilme potansiyeli vardır.

Anahtar Kelimeler

• ADAMTS9
• ADAMTS15
• Psoriasis
• Psoriatik Artrit

Destekleyen Kurum

TÜBİTAK ve DÜBAP

Proje Numarası

(TÜBİTAK) 214S024 (DÜBAP) Tıp.16.024

Teşekkür

Prof. Dr Kemal Nas, Prof Dr Remzi Çevik ve Prof. Dr. Bilal Sula’ ya hasta örneklerini sağlamadaki katkılarından dolayı teşekkür ederiz.

Kaynakça

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