title: Evaluation of Signaling Pathways Involved in γ-Globin Gene Induction Using Fetal Hemoglobin Inducer Drugs.
abstract: Potent induction of fetal hemoglobin (HbF) production results in alleviating the complications of β-thalassemia and sickle cell disease (SCD). HbF inducer agents can trigger several molecular signaling pathways critical for erythropoiesis. Janus kinase/Signal transducer and activator of transcription (JAK/STAT), mitogen activated protein kinas (MAPK) and Phosphoinositide 3-kinase (PI3K) are considered as main signaling pathways, which may play a significant role in HbF induction. All these signaling pathways are triggered by erythropoietin (EPO) as the main growth factor inducing erythroid differentiation, when it binds to its cell surface receptor, erythropoietin receptor (EPO-R) HbF inducer agents have been shown to upregulate HbF production level by triggering certain signaling pathways. As a result, understanding the pivotal signaling pathways influencing HbF induction leads to effective upregulation of HbF. In this mini review article, we try to consider the correlation between HbF inducer agents and their molecular mechanisms of γ-globin upregulation. Several studies suggest that activating P38 MAPK, RAS and STAT5 signaling pathways result in efficient HbF induction. Nevertheless, the role of other erythroid signaling pathways in HbF induction seems to be indispensible and should be emphasized.
authors: Toxicology Research Center, Ahvaz University of Medical Sciences, Ahvaz, Iran.
authors: Fakher
authors: F
authors: Rahim
authors: General Practitioner, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors: Hossein
authors: H
authors: Allahmoradi
authors: Research Center of Thalassemia & Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors: Fatemeh
authors: F
authors: Salari
authors: Department of Hematology and Blood Banking, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors: Mohammad
authors: M
authors: Shahjahani
authors: Sarem Cell Research Center- SCRC, Sarem Women's Hospital, Tehran, Iran.
authors: Ali Dehghani
authors: AD
authors: Fard
authors: Department of nutrition, Allied Health Sciences School, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors: Seyed Ahmad
authors: SA
authors: Hosseini
authors: Research Center of Thalassemia & Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors: Hadi
authors: H
authors: Mousakhani
keywords: Fetal hemoglobin; Sickle cell disease; β-thalassemia