title: The Impact of Growth Hormone Therapy on the Apoptosis Assessment in CD34+ Hematopoietic Cells from Children with Growth Hormone Deficiency.
abstract: Growth hormone (GH) modulates hematopoietic cell homeostasis and is associated with apoptosis control, but with limited mechanistic insights. Aim of the study was to determine whether GH therapeutic supplementation (GH-TS) could affect apoptosis of CD34+ cells enriched in hematopoietic progenitor cells of GH deficient (GHD) children. CD34+ cells from peripheral blood of 40 GHD children were collected before and in 3rd and 6th month of GH-TS and compared to 60 controls adjusted for bone age, sex, and pubertal development. Next, apoptosis assessment via different molecular techniques was performed. Finally, to comprehensively characterize apoptosis process, global gene expression profile was determined using genome-wide RNA microarray technology. Results showed that GH-TS significantly reduced spontaneous apoptosis in CD34+ cells (p< 0.01) and results obtained using different methods to detect early and late apoptosis in analyzed cells population were consistent. GH-TS was also associated with significant downregulation of several members of TNF-alpha superfamily and other genes associated with apoptosis and stress response. Moreover, the significant overexpression of cyto-protective and cell cycle-associated genes was detected. These findings suggest that recombinant human GH has a direct anti-apoptotic activity in hematopoietic CD34+ cells derived from GHD subjects in course of GH-TS.
authors.affiliation: Department of General Pathology, Pomeranian Medical University in Szczecin, 72 Powstancow Wlkp. Street, 70-111 Szczecin, Poland. kawamilosz@gmail.com.
authors.forename: Miłosz Piotr
authors.initials: MP
authors.lastname: Kawa
authors.affiliation: Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases and Cardiology of the Developmental Age, Pomeranian Medical University in Szczecin, 1 Unii Lubelskiej Street, 71-252 Szczecin, Poland. iwona.stecewicz@wp.pl.
authors.forename: Iwona
authors.initials: I
authors.lastname: Stecewicz
authors.affiliation: Department of General Pathology, Pomeranian Medical University in Szczecin, 72 Powstancow Wlkp. Street, 70-111 Szczecin, Poland. ka.kaczynska@gmail.com.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Piecyk
authors.affiliation: Department of General Pathology, Pomeranian Medical University in Szczecin, 72 Powstancow Wlkp. Street, 70-111 Szczecin, Poland. edyta.paczkowska@pum.edu.pl.
authors.forename: Edyta
authors.initials: E
authors.lastname: Paczkowska
authors.affiliation: Department of General Pathology, Pomeranian Medical University in Szczecin, 72 Powstancow Wlkp. Street, 70-111 Szczecin, Poland. doroginska@gmail.com.
authors.forename: Dorota
authors.initials: D
authors.lastname: Rogińska
authors.affiliation: Department of General Pathology, Pomeranian Medical University in Szczecin, 72 Powstancow Wlkp. Street, 70-111 Szczecin, Poland. ania.sobus@gmail.com.
authors.forename: Anna
authors.initials: A
authors.lastname: Sobuś
authors.affiliation: Department of General Pathology, Pomeranian Medical University in Szczecin, 72 Powstancow Wlkp. Street, 70-111 Szczecin, Poland. karolinaluczkowska58@gmail.com.
authors.forename: Karolina
authors.initials: K
authors.lastname: Łuczkowska
authors.affiliation: Department of General Pathology, Pomeranian Medical University in Szczecin, 72 Powstancow Wlkp. Street, 70-111 Szczecin, Poland. ewapius@wp.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Pius-Sadowska
authors.affiliation: Department of Pediatric and Oncological Surgery, Pomeranian Medical University in Szczecin, 1 Unii Lubelskiej Street, 71-252 Szczecin, Poland. chirurgia.dziecieca@op.pl.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Gawrych
authors.affiliation: Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases and Cardiology of the Developmental Age, Pomeranian Medical University in Szczecin, 1 Unii Lubelskiej Street, 71-252 Szczecin, Poland. petrela1@wp.pl.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Petriczko
authors.affiliation: Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases and Cardiology of the Developmental Age, Pomeranian Medical University in Szczecin, 1 Unii Lubelskiej Street, 71-252 Szczecin, Poland. klchrdz2@pum.edu.pl.
authors.forename: Mieczysław
authors.initials: M
authors.lastname: Walczak
authors.affiliation: Department of General Pathology, Pomeranian Medical University in Szczecin, 72 Powstancow Wlkp. Street, 70-111 Szczecin, Poland. machalin@pum.edu.pl.
authors.forename: Bogusław
authors.initials: B
authors.lastname: Machaliński
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002452:Cell Count; D002648:Child; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D013006:Growth Hormone / Q000172:deficiency* / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D008297:Male; D011986:Receptors, Somatotropin / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D011986:Receptors, Somatotropin; D013006:Growth Hormone
keywords: CD34+ cells; apoptosis; apoptosis control; cell death; growth hormone deficiency; growth hormone deficiency in children; hematopoiesis; hematopoietic progenitor cells