Investigation of pathogenesis and progression of interstitial disorder mediated by FcRn in glomerulonephritis.

点击翻译按钮获取中文摘要

In the kidney, proteins filtered through glomeruli are reabsorbed by endocytosis along the proximal tubules to avoid renal loss of large amounts of proteins such as albumin, β_2-microglobulin and several hormones. Although the reabsorption of albumin prevents the loss of large amounts of this major plasma protein via the urine, excess reabsorption of albumin may be a factor for the development and progression of chronic renal diseases. Thus, the kidney appears to have a limit on the amount of protein which can be reabsorbed and catabolized at the greatly increased filtered-loads found in renal diseases. On the other hand, immunoglobulins such as IgG, IgA, and their fragments have also been found in the urine. Similar to other proteins, absorption of these molecules seems to be regulated by the endocytosis pathway in the proximal tubules, but the mechanisms are not fully understood. A recent study revealed that the neonatal Fc receptor (FcRn), which is involved in the transport of IgG a … More cross several epithelial and endothelial cells, was expressed in renal proximal tubular epithelial cells. It was suggested that FcRn may play an important role in the reabsorption of IgG from the tubular fluid. However, to date there is no direct evidence for receptor-mediated endocytosis of IgG in the renal proximal tubular epithelial cells in humans. To explore the physiological roles of FcRn in the proximal tubules, we examined IgG transport using human renal proximal tubular epithelial cells (RPTECs). FcRn was expressed in RPTECs and physically associated with β_2-microglobulin, preserving the capacity of specific pH-dependent IgG binding Human IgG was bound to the cell surface of RPTECs in a pH-dependent manner. The human IgG transport assay revealed that receptor-mediated transepithelial transport of intact IgG in RPTECs was bidirectional and that it requires the formation of acidified intracellular compartments. Using double immunofluorescence, internalized human IgG was shown to be marked in cytoplasm of RPTECs and colocalized with FcRn. There data define the mechanisms of FcRn-associated IgG transport in the RPTEC monolayers. Less