Protein Malnutrition Induces Bone Marrow Mesenchymal Stem Cells Commitment to Adipogenic Differentiation Leading to Hematopoietic Failure

Autor(es)

Ramos Cunha, Mayara Caldas ^[1] ; Lima, Fabiana da Silva ^[1] ; Ramirez Vinolo, Marco Aurelio ^[2] ; Hastreiter, Araceli ^[1] ; Curi, Rui ^[3] ; Borelli, Primavera ^[1] ; Fock, Ricardo Ambrosio ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Clin & Toxicol Analyses, Sao Paulo - Brazil

^[2] Univ Campinas Unicamp, Inst Biol, Dept Genet Evolut & Bioagents, Campinas - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 8, n. 3 MAR 14 2013.
• Citações Web of Science: 23

Resumo

Protein malnutrition (PM) results in pathological changes that are associated with peripheral leukopenia, bone marrow (BM) hypoplasia and alterations in the BM microenvironment leading to hematopoietic failure; however, the mechanisms involved are poorly understood. In this context, the BM mesenchymal stem cells (MSCs) are cells intimately related to the formation of the BM microenvironment, and their differentiation into adipocytes is important because adipocytes are cells that have the capability to negatively modulate hematopoiesis. Two-month-old male Balb/c mice were subjected to protein-energy malnutrition with a low-protein diet containing 2% protein, whereas control animals were fed a diet containing 12% protein. The hematopoietic parameters and the expression of CD45 and CD117 positive cells in the BM were evaluated. MSCs were isolated from BM, and their capability to produce SCF, IL-3, G-CSF and GM-CSF were analyzed. The expression of PPAR-gamma and C/EBP-alpha as well as the expression of PPAR-gamma and SREBP mRNAs were evaluated in MSCs together with their capability to differentiate into adipocytes in vitro. The malnourished animals had anemia and leukopenia as well as spleen and bone marrow hypoplasia and a reduction in the expression of CD45 and CD117 positive cells from BM. The MSCs of the malnourished mice presented an increased capability to produce SCF and reduced production of G-CSF and GM-CSF. The MSCs from the malnourished animals showed increased expression of PPAR-gamma protein and PPAR-gamma mRNA associated with an increased capability to differentiate into adipocytes. The alterations found in the malnourished animals allowed us to conclude that malnutrition committed MSC differentiation leading to adipocyte decision and compromised their capacity for cytokine production, contributing to an impaired hematopoietic microenvironment and inducing the bone marrow failure commonly observed in protein malnutrition states. (AU)

• Processo FAPESP: 10/51747-0 - Influencia da desnutricao proteica-energetica sobre a expressao de fatores de transcricao envolvidos no processo de diferenciacao de celulas tronco mesenquimal medular
• Beneficiário: Ricardo Ambrósio Fock
• Modalidade de apoio: Auxílio à Pesquisa - Regular