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Type: Artigo de periódico
Title: Serine Protease Inhibitor Kunitz-type 2 Is Downregulated In Myelodysplastic Syndromes And Modulates Cell-cell Adhesion.
Author: Roversi, Fernanda Marconi
Lopes, Matheus Rodrigues
Machado-Neto, João Agostinho
Longhini, Ana Leda F
Duarte, Adriana da Silva Santos
Baratti, Mariana Ozello
Palodetto, Bruna
Corrocher, Flávia Adolfo
Pericole, Fernando Vieira
Campos, Paula de Melo
Favaro, Patricia
Traina, Fabiola
Saad, Sara Teresinha Olalla
Abstract: Myelodysplastic syndromes (MDS) are clonal disorders involving hematopoietic stem cells (HSC) characterized by ineffective hematopoiesis. In addition to HSC defects, a defective hematopoiesis supporting capacity of mesenchymal stromal cells (MSCs) in the microenvironment niche has been implicated in MDS pathophysiology. The interaction between the dysfunctional MSCs MDS and HSC regulates diverse adhesion-related processes, such as progenitor cell survival, proliferation, differentiation, and self-renewal. As previously reported, a microarray analysis identified serine protease inhibitor kunitz-type 2 (SPINT2), an inhibitor of hepatocyte growth factor (HGF) activation, to be downregulated in MSCs from MDS patients. To define the role of SPINT2 in MDS hematopoietic microenvironment, an analysis of the effect of SPINT2 silencing in MSCs was carried out. We herein reported significantly lower levels of SPINT2 whereas HGF was expressed at higher levels in MSCs from MDS patients compared with healthy controls. SPINT2 underexpression results in an increased expression, production, and secretion of HGF and stromal cell-derived factor 1 (SDF-1) by MSCs. An increased adhesion of normal HSC or malignant cells onto MSCs silenced for SPINT2 was also observed. The altered MSCs adhesion in SPINT2-knockdown cells was correlated with increased CD49b and CD49d expression and with a decrease in CD49e expression. Our results suggest that the SPINT2 underexpression in the MSC from MDS patients is probably involved in the adhesion of progenitors to the bone marrow niche, through an increased HGF and SDF-1 signaling pathway.
Subject: Adolescent
Cell Adhesion
Cell Proliferation
Cell Survival
Cells, Cultured
Chemokine Cxcl12
Gene Knockdown Techniques
Hematopoietic Stem Cells
Hepatocyte Growth Factor
Integrin Alpha5
Membrane Glycoproteins
Mesenchymal Stromal Cells
Middle Aged
Myelodysplastic Syndromes
Citation: Stem Cells And Development. v. 23, n. 10, p. 1109-20, 2014-May.
Rights: fechado
Identifier DOI: 10.1089/scd.2013.0441
Date Issue: 2014
Appears in Collections:Unicamp - Artigos e Outros Documentos

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