Alterations in proteins of bone marrow extracellular matrix in undernourished mice

Abstract

The objective of the present study was to determine the effect of protein malnutrition on the glycoprotein content of bone marrow extracellular matrix (ECM). Two-month-old male Swiss mice were submitted to protein malnutrition with a low-protein diet containing 4% casein as compared to 20% casein in the control diet. When the experimental group had attained a 20% loss of their original body weight, we extracted the ECM proteins from bone marrow with PBS buffer, and analyzed ECM samples by SDS-PAGE (7.5%) and ECL Western blotting. Quantitative differences were observed between control and experimental groups. Bone marrow ECM from undernourished mice had greater amounts of extractable fibronectin (1.6-fold increase) and laminin (4.8-fold increase) when compared to the control group. These results suggest an association between fluctuations in the composition of the hematopoietic microenvironment and altered hematopoiesis observed in undernourished mice.

Protein-energy malnutrition halts hemopoietic progenitor cells in the G0/G1 cell cycle stage, thereby altering cell production rates

“…This is combined with a smaller number of cells exhibiting CD34 + , CD45 + and CD117 + . We conclude that this is one of the factors responsible for the marrow hypoplasia observed here, partially explaining our results (27,28).…”

“…Cytokine-related stimulation allows the overexpression of this receptor. The abnormalities found in ECM components could alter the co-localization of the diverse growth factors and cytokines, which are required to modulate the growth and differentiation process of hematopoietic cells (12,28,35). This in turn may alter the cell-cell and cell-ECM interactions, thereby modifying the signaling pathways and leading to bone marrow hypoplasia with a depletion of progenitor hematopoietic populations and peripheral pancytopenia.…”

Haematological alterations in protein malnutrition

“…45,46,47 One can see that haemopoiesis is a complex and highly regulated phenomenon which depends on (i) the existence of primitive cells with a proliferative capability; (ii) the regulatory action of growth factors; (iii) the components of the microenvironment and (iv) the architectural structure of this microenvironment. 48,49,50 Concepts acquired on the effect of human protein privation have largely been based on information obtained from severely malnourished individuals, suffering multiple nutritional deficiencies, or from patients with chronic systemic diseases in which the effects of the disease and its therapy are difficult to distinguish from those of nutritional deficiency. Data obtained in animals have, as we see it, allowed a partial evaluation of the production, mobilisation and function of phagocytes.…”

PTHrP increases transcriptional activity of the integrin subunit α5

“…Parathyroid hormone-related protein expression in MDAMB231 cells demonstrated a correlation with adhesion to collagen type I, fibronectin and laminin. Bone is comprised of 95% collagen type I, with fibronectin and laminin present within the bone marrow ECM (Vituri et al, 2000) and laminin also a key component of the sinusoidal basement membrane (Gu et al, 2003), so the upregulation of integrins that bind to these ECM components may explain the fact that breast cancer cells predominately metastasise to bone (Powell et al, 1991). Hepatic sinusoidal endothelial cells do not possess a basement membrane but both fibronectin and collagen type I are prevalent in the space of Disse, which separates hepatocytes from sinusoids (Martinez-Hernandez and Amenta, 1995), so cells which have an increased ability to adhere to fibronectin and collagen type I (like the PTHrP expression profile of the HT29 cell line described in this report) but not laminin, may exhibit preferential metastasis to the liver rather than bone.…”