17β-Estradiol melindungi epitel esofagus dari disfungsi dan remodeling pada penderita esofagitis eosinofilik (EoE)

wp-1517304736062..jpg17β-Estradiol melindungi epitel esofagus dari disfungsi dan remodeling pada penderita esofagitis eosinofilik (EoE)

Audi Yudhasmara, Widodo Judarwanto

Insiden esofagitis eosinofilik (EoE) lebih besar pada subjek laki-laki daripada perempuan, dan dasar molekuler yang mendasari untuk bias jenis kelamin ini masih belum jelas. beberapa peneliti berusaha menggambarkan kontribusi hormon seks estrogen terhadap fenotipe EoE dan fungsi penghalang epitel esofagus dan remodeling.

Telah dilakukan penelitian tentang analisis demografi dan kejadian EoE pada subjek pria dan wanita dari kohort pediatrik pusat-tunggal. Analisis ekspresi gen responsif-estrogen dan pewarnaan estrogen reseptor (ESR) imunofluoresensi spesimen biopsi esofagus dari pasien dengan EoE dan subyek kontrol dilakukan. Efek dari 17β-estradiol (E2) pada jalur pensinyalan yang diinduksi IL-13, ekspresi gen, dan arsitektur epitel esofagus dan fungsi penghalang dalam sistem kultur sel keratinosit kerongkongan manusia (EPC2) manusia utama (EPC2-air-liquid interface) dilakuka pemeriksaan.

Peneliti mengamati dominasi laki-laki pada pasien dengan EoE. Analisis set data sekuensing RNA mengungkapkan disregulasi yang signifikan dari jaringan gen responsif-estrogen dan ekspresi ESR1 dan ESR2 dalam spesimen biopsi esofagus dari pasien dengan EoE dibandingkan dengan subyek kontrol. Stimulasi IL-13 dari sel-sel antarmuka EPC2-udara-cair menyebabkan arsitektur seluler diubah dengan pelebaran terinduksi ruang antar sel dan disfungsi penghalang. Pretreatment EPC2s dengan E2 sebelum paparan IL-13 mencabut perubahan arsitektur yang diinduksi IL-13 dan disfungsi penghalang esofagus. Secara mekanis, efek protektif E2 bergantung pada ESR2 dan berhubungan dengan berkurangnya tirosin kinase 2 yang diinduksi IL-13 dan transduser sinyal dan aktivator transkripsi 6 fosforilasi dan ekspresi gen yang disegulasi EoE.

Gen responsif estrogen dimodifikasi pada pasien dengan EoE dibandingkan dengan subyek kontrol. E2 melemahkan perubahan arsitektur yang diinduksi IL-13 dan disfungsi penghalang epitel esofagus melalui penghambatan IL-13 / tirosin kinase 2 / transduser sinyal dan aktivator jalur transkripsi 6 melalui proses yang bergantung pada ESR2. Pensinyalan hormon estrogen dapat melindungi terhadap perkembangan EoE pada subjek wanita.

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