| Neonatal Fc receptor (FcRn), responsible for transferring IgG, was firstly found expression at intestine epithelial cells of neonatal mice. In human beings, FcRn was firstly found expressed at Syncytial trophoblast of pregnant women. Through mediation of FcRn, IgG could be brought into the circulation of newborn infants. Furthermore, FcRn could also expressed at liver, breast, lung, intestine and endothelial cell and modulate the transferring of IgG in these sites. While FcRn expressed in endothelial cell and hematopoietic cell play a crucial rule at the stablising of the concentration of FcRn and prolong its half life in blood.Haymann JP found in2000that FcRn was expressed at podocyte of kidney while messangial cell did not express this receptor, however the function of FcRn in kidney remains unclear. Plenty studies have proved FcRn could reduce degradation and prolong the half life of IgG in circulation. For autoimmune diseases such as myasthenia gravis, blocking the function of FcRn could relieve the pathogenetic condition. It is well known that kinds of glomerular nephritis belongs to the category of autoimmune diseases. Immune complex deposion at glomeruli have been regarded as the significant mechnisms of kinds of nephritis like lupu nephritis, acute diffuse proliferative glomerular nephritis and so on. Our former work has revealed that antithymocyte serum could stimulated the high expression of FcRn in podocyte when podocyte-messangial cells co-cultureed together. This work proved that Immune complex played a role at the up-regulation of FcRn.Presently, there is no report about whether the expression of FcRn alternated in human glomerular nephritis(GN). In this study, We collected89specimens of human kidney microamount biopsy, including lupus nephritis (LN), acute diffuse proliferative glomerular nephritis (APGN), membranous nephropathy (MN), IgA nephropathy (IgAN), minimal change disease (MCD) and so on, and took nephridial tissue adjacent to cancer as normal control. The expression of FcRn in nephridial tissue was detected by immunohistochemistry. As a result, FcRn was discovered to express in renal glomerulus podocyte, and the expression of FcRn in LN, APGN was significantly higher than normal nephridial tissue, the expression of FcRn in MN, IgAN was also higher than normal, but the change in MCD was not obviously. Simultaneously, we collected46specimens of fresh kidney microamount biopsy, obtained purified renal glomerulus with laser capture microdissection technology (LCM), extracted RNA, and detected the variance of FcRn mRNA expression with the method of Real-time RT-PCR, and the result was coincident with immunohistochemistry. In addition, we inspected the expression level of FcRn with immunohistochemistry in mesangial proliferative nephritis rat model (thy-1GN), MN rat model (Heymann GN) and LN mouse model, and discovered that the expression of FcRn in the three GN models was obviously up-regulated than normal rat or mouse.To verify the up-regulation effect of immune complex (IC) to FcRn in advance, we used podocyte-mesangial cells co-culture model in vitro to simulate the action of IC to podocyte, and observed that the expression of FcRn increased significantly with western blot and flow cytometry technology. In addition, several inflammatory factors were known to be enhanced expression in GN, like TNF-a. After observed the affect of inflammatory factor TGF-β to FcRn expression, we found that the expression of FcRn in podocyte increased after the stimulus of TGF-β.As stated previously, our study confirmed the up-regulation of FcRn expression in GN mediated by IC, at the same time, TGF-β may participated in the regulation of FcRn. And consequence of the up-regulation of FcRn might be involved in the occurrence and development of GN. |
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