An Investigation into the Multifunctional Nature of Renal Pericytes

Emerging evidence shows vascular resident pericytes are multifunctional, with involvement in inflammation and immune cell infiltration in addition to their well characterised functions in angiogenesis and the regulation of vascular stability and perfusion. Similar to pericytes from animal models, cultured human pericytes are able to produce inflammatory mediators, and renal pericytes show active involvement in the recruitment and direction of immune cells. This has big implications for the treatment of renal disease, where loss of pericytes and marked inflammation are associated with poor patient outcomes. However, the nature of this pericyte-mediated inflammation varies between animals and humans, and tissue culture does not always accurately reflect in vivo behaviour. Further still, the means by which inflammatory involvement if pericytes is identified may be misattributed; with a known overlap in cell-surface molecule expression between pericytes and macrophage (MΦ). Proper identification of pericytes and thus their multifunctionality is imperative. The hypothesis behind this investigation is that renal pericytes in in situ kidney slices reflect in vivo physiology and are multifunctional, distinguishable from MΦ, and involved in renal inflammation. The utilisation of both rodent and murine in situ “live” kidney slices will enable investigations into this phenomenon by enabling use of colabelling with overlapping pericyte (NG2 and PDGFR-β) and MΦ (CD163 and F4/80) markers, maintaining in vivo cellular communications, and visualisation of notable cell morphology. Overall, this thesis presents data to support kidney slices accurately modelling in vivo vascular physiology and thus other pericyte-mediated functions. Furthermore, this data supports renal pericytes exhibiting multifunctionality, notably in a cell-surface molecule-specific manner that is conserved across species. While not investigated in this thesis it is hoped these findings may translate to human physiology providing novel therapeutic targets against the progression of renal disease.