Mesangial cells: renal function protagonists or coadjuvants?

In order to achieve homeostasis, each kidney has about one million nephrons made up of different types of cells and tissues. The functional harmony of the cells of the renal parenchyma relies on a sophisticated bio-automation network devised to ensure the order and effectiveness of integrated biological responses. Mesangial cells (MC) and the mesangial matrix were first described in the mid-nineteenth century, as the components of a region called glomerular mesangium (between vessels). For a long time mesangial cells were analyzed by optical microscopy and considered merely as histological structures developed to provide axial support for capillary loops within the glomeruli. In 1951, Homer Smith1 referred to mesangial cells as “a rare third cell type present in the glomerulus, located in the intercapillary axial structure”. In light of current research tools, mesangial cells are seen as a special form of microvascular pericytes, which combine to form a mesangium/endothelium/epithelium functional integration unit. Strategically located, mesangial cells are directly involved in biological phenomena governing renal physiology and embryology. In this triply integrated circuit, changes occurring in one cell type can produce corresponding effects in others. The interactions result in “cross-talking” modulated by signaling pathways which include gap junctions, hormones, cytokines and chemokines.2 MC contractile properties allow them to participate in the control of intraglomerular capillary blood flow, glomerular ultrafiltration area and, consequently, individual nephron glomerular filtration rates (Figure 1). Mesangial cells produce structural components of the glomeruli, vasoactive agents, growth factors, cytokines, chemokines, erythropoietin, and elements of the complement system.2 In terms of paracrine effects, mesangial cells express receptors for different vasoactive agents, growth factors, adhesion molecules, chemokines, and cytokines, among others. This set of factors physiologically assigns mesangial cells roles in functional regulation and remodeling of renal tissue. Modern research tools have yielded a significant number of in vitro and in vivo experiments which revealed the active role of mesangial cells in different pathophysiological processes affecting the nephrons. One of the most relevant is the relationship between MC proliferation and the subsequent development of the mesangial matrix, observed in immune and non-immune glomerular injuries, particularly the pathophysiology of diabetic nephropathy.3 Closer analysis of the glomeruli has shown that mesangial cells are not completely homogeneous. As many as 10% of them have different phenotypes when compared to other mesangial cells, in addition to presenting phagocytic behavior, expressing surface markers and cytokines found only in immune system cells, for which reason they were named myeloid dendritic cells.4 Mesangial cells also