Role of GPR109A in psoriasis

master's thesis

• Title (croatian): Uloga GPR109A receptora u psorijazi
• Author: Lucija Leko
• Mentor: Igor Stuparević (mentor)
• Committee member: Višnja Besendorfer (predsjednik povjerenstva)
• Committee member: Kristina Radošević (član povjerenstva)
• Committee member: Igor Stuparević (član povjerenstva)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Chemistry and Biochemistry); (Laboratory for Biochemistry); Zagreb
• Defense date and country: 2023-07-03, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology

Abstract

Psoriasis is a chronic, inflammatory skin disease characterized by keratinocyte hyperproliferation and immune cell infiltration. In this study, bioinformatic analysis showed that HCAR2, human gene encoding a short-chain fatty acid receptor GPR109A, was expressed in keratinocytes and macrophages in lesioned skin of psoriatic patients. In imiquimod (IMQ) induced mouse model immunostaining showed GPR109A to be located in keratinocytes and dermal inflammatory cells. We showed that Hcar2 expression was affected in IMQ-induced mouse model and that mice lacking GPR109A had an aggravated psoriasis-like phenotype. Levels of inflammatory mediators like MPO, LCN2 and IL-1β were elevated along with Il-17a expression, all indicating GPR109A has a protective role in psoriasis. Further research should focus on using GPR109A agonists, such as butyrate, as potential therapeutics in treatment of psoriasis.

Abstract (croatian)

Psorijaza je kronična, upalna, kožna bolest karakterizirana hiperproliferacijom keratinocita i infiltracijom stanica imunološkog sustava u kožu. U ovom istraživanju, bioinformatička analiza je pokazala da je HCAR2, ljudski gen koji kodira za receptor kratkolančanih masnih kiselina GPR109A, izražen u keratinocitima i makrofagima u oštećenoj koži pacijenata s psorijazom. Imunohistokemijsko bojanje u mišjem imikvimod (IMQ) tretiranom modelu pokazalo je da je GPR109A prisutan u keratinocitima i infiltracijskim stanicama imunološkog sustava dermisa. Pokazali smo da je ekspresija gena Hcar2 izmjenjena u mišjem IMQ tretiranom modelu te da miševi koji nemaju GPR109A imaju pogoršan psorijatični fenotip. Razine upalnih medijatora poput MPO, LCN2 i IL-1β su povišene zajedno s ekspresijom Il-17a, što sve ukazuje na zaštitnu ulogu GPR109A u psorijazi. Daljnja istraživanja trebala bi se usredotočiti na upotrebu agonista GPR109A, poput butirata, kao potencijalne terapije u liječenju psorijaze.

• Keywords: psoriasis; imiquimod (IMQ) mouse model; GPR109A; Hcar2; skin inflammation
• Keywords (croatian): psorijaza; imikvimod (IMQ) mišji model; GPR109A; Hcar2; upala kože
• Language: english
• URN:NBN: urn:nbn:hr:159:730726
• Study programme: Title: Molecular Biotechnology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka molekularne biotehnologije (magistar/magistra inženjer/inženjerka molekularne biotehnologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-04-29 10:57:06