Kidney cell mechanotransduction in response to sustained hydrostatic pressure

Several kidney pathologies result in elevated pressures within the renal interstitial fluid, affecting cell function and gene expression. The long-term objective of this research was, therefore, to elucidate the signaling cascades involved in kidney cell responses to hydrostatic (physiological and/or pathological) pressures. Initial in vitro studies were performed on two kidney cell lines (tubular and medullary) to determine changes in cell proliferation, cytoskeletal (specifically, microfilament and microtubule) arrangement, and mRNA expression (of cell signaling genes such as G_α, G_β, c-jun, and c-fos) following exposure to pathological (60 cmH₂O) pressures. Proliferation studies provided evidence that exposure to pressures of 60 cmH₂O resulted in increased renal cell proliferation (compared to controls cells under 0.3 cmH₂O) after 7 days. In addition to increased cell proliferation, time-dependent changes in individual microfilament structures took place in response to the pressure stimulus. These results prove that hydrostatic pressure alters the function of tubular and medullary cells; more importantly, microfilaments were involved in the signaling mechanism of this response. Additionally, preliminary results suggest that G_α, G_β, c-jun, and c-fos are up-regulated in renal cells following exposure to 60 cmH₂O pressure. Uncovering this signaling cascade in renal cells may aid in the design of novel, targeted drug therapies for kidney pathologies.