BMP-7 Modulates Hyaluronan-Mediated Proximal Tubular Cell-Monocyte Interaction

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Abstract
Increased synthesis of hyaluronan (HA) in the renal corticointerstitium has been documented in renal injury, although the functional significance of this is unclear. The aim of the work presented in the current study was to examine the role of HA in monocyte binding by proximal tubular cells (PTC). Using the PTC line HK-2, the authors show that unstimulated cells formed pericellular HA cable-like structures that bound mononuclear leukocytes via their cell surface CD44. Stimulation with bone morphogenic protein–7 (BMP-7) led to increased formation of HA cable-like structures and also a dose-dependent increase in CD44-dependent binding of radiolabeled U937 cells. The authors have previously demonstrated that stimulation with IL-1β is a potent stimulus for induction of HAS gene expression and HA synthesis. In this study, addition of IL-1β influenced neither HA cable formation nor CD44-mediated monocyte binding. Rather IL-1β led to an increase in intercellular adhesion molecule (ICAM)–dependent monocyte binding. Characterization of HA synthesis by addition of [3H]-glucosamine to cells at the time of stimulation demonstrated that increased HA in response to IL-1 was most apparent in the culture medium, while BMP-7 led to an increase in cell associated HA. Stimulation of cells with BMP-7 induced HAS2 mRNA expression and decreased the expression of Hyal1 and Hyal2. In contrast to BMP-7, IL-1β did not influence Hyal expression. The data presented in this manuscript provide insight into how alterations in HA synthesis in the renal cortex may be involved in modulation of the interaction between infiltrating inflammatory cells and resident cells.