Pigment Epitel Kaynaklı Faktör (PEDF): Çok Yönlü ve Fonksiyonlu Yeni Bir Terapötik Ajan

Pigment epitel kaynaklı faktör, non-inhibitör serin proteaz inhibitör (serpin) ailesinin bir üyesi olup doğal oluşan bir proteindir. İnsan pigment epitel kaynaklı faktör geni 17. kromozom üzerinde lokalize olmuş ~yaklaşık 16 kb uzunluğunda bir gendir. Olgun gen ürünü çoğunlukla 50 kDa ağırlığında çözünür monomerik bir glikoprotein olarak salınmaktadır. Mevcut çalışmalar pigment epitel kaynaklı faktörünün sadece gözdeki retinal pigment epitel hücrelerinde değil, insan vücudunda ve hemen hemen tüm memeli dokularında da ifade olduğunu göstermektedir. Pigment epitel kaynaklı faktör ilk defa retinal pigment epitelyal hücrelerinden salınan, retinoblastoma hücrelerinin farklılaşmasını indükleyen nörotrofik bir faktör olarak keşfedilmiştir. Fakat sonraları pigment epitel kaynaklı faktörünün çok sayıda ve çeşitli biyolojik aktivitelere sahip olduğu ortaya çıkmıştır. Bu ilginç proteinin antianjiyogenez, antiproliferatif, tümör hücre farklılaşması, anti-oksidan ve nöroprotektif etkileri gibi eşsiz tıbbi özellikleri vardır. Tüm bu etkiler, son zamanlarda pigment epitel kaynaklı faktörünü araştırma konularının ilgi odağı haline getirmiştir. Bugünlerde çalışmalar pigment epitel kaynaklı faktörünün dolaylı (anti-anjiyogenez) ve direk anti-tümör etkileri (hücre bölünmesinin, tümör invazyonunun ve metastazın inhibisyonu, tümör hücre apoptoz ve farklılaşmasını teşviki gibi) üzerine yoğunlaşmıştır. Bu nedenle pigment epitel kaynaklı faktör, tümör hücrelerini hedef alabilen ve gelecekte geleneksel kemoterapinin yerine kullanılabilecek umut vaat eden bir anti-tümör ajanı olarak görülmektedir. Bu derlemede; Pigment epitel kaynaklı faktörünün yapısı ve fonksiyonlarından kısaca bahsedilerek, etkin rol oynadığı mekanizmalara değinilecektir.

Anahtar Kelimeler:

Pigment epitel kaynaklı faktör (PEDF), anti-anjiyogenez

Pigment Epithelium-Derived Factor (PEDF): A Multifaceted and Functional New Therapeutic Agent

Pigment epithelium-derived factor, a noninhibitory member of the serine protease inhibitor (serpin) family, is a naturally-occurring protein. The gene encoding human pigment epithelium-derived factor was localized to 17th chromosome and is around 16 kb. Mature gene product is 50 kDa and secreted as a soluable monomeric glycoprotein. Current studies show that pigment epithelium-derived factor is not only found in retinal pigment epithelium cells, but also widely expressed throughout the human body and in the tissues of almost all mammals. Pigment epithelium-derived factor was first discovered as a neurotrophic factor, an inducer of retinoblastoma cell differentiation, secreted by retinal pigment epithelial cells. Later, multiple and varied biological activities of pigment epithelium-derived factor have been found. The unique medicinal properties of this interesting protein are; anti-angiogenesis, anti-proliferative, tumor cell differentiation, anti-oxidant, and neuroprotective effects. Due to all these effects, recently pigment epithelium-derived factor has become the focus of attention of research topics. Today, studies focus on pigment epithelium-derived factor’s indirect (anti-angiogenesis) and direct antitumor effects (inhibiting cell division, tumor invasion and metastasis, promoting tumor cell apoptosis and differentiation). Thus, it is an emerging anti-tumor agent that may be able to target tumor cells and may be used instead of conventional chemotherapy in the future. In this review; briefly the structure and functions of pigment epithelium-derived factor, and the mechanisms in which pigment epithelium-derived factor plays an active role will be discussed.

Keywords:

Pigment epithelium-derived factor (PEDF), anti-angiogenesis,

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