Our results suggest that qualitative and quantitative changes of serum IgA are determined at the level of stem cells, and that BMT from normal donors can attenuate glomerular lesions in HIGA mice. This approach may offer a new avenue to study the pathogenesis of IgA nephropathy.
To understand the role of mesangial matrix in regulating responses of mesangial cells (MCs), particularly as a cause of disease, we examined the behavior of MCs cultured in a three-dimensional extracellular matrix (ECM). Mouse and rat MCs were incorporated into ECM composed of type I collagen gel matrix (CGM) and basement membrane-type gel matrix (BGM), and their shape and proliferation were assessed. The effect of gel matrix on MC migration was also studied. MCs exhibited marked elongation and proliferation in CGM, whereas these behavior were inhibited by increasing the ratio of BGM. Although CGM allowed MC migration, BGM restricted it to a great extent. To identify the cause of our findings, we examined the effects of ECM components in our experimental system. Laminin, fibronectin, type IV collagen, and heparin-like proteoglycans (heparan sulfate and heparin) were each mixed separately with CGM at a concentration of 50 micrograms/ml gel. Whereas fibronectin promoted MC elongation and proliferation, and laminin inhibited MC migration, type IV collagen and heparin-like proteoglycans inhibited all three activities of MCs. Our findings suggest that basement membrane-type mesangial matrix is important in regulating the behavior of MCs in vivo.
Background. Senescence marker protein-30 (SMP30), a calcium binding protein, is preferentially expressed in the renal proximal tubules and hepatocytes and is presumed to play a role in Ca 2ϩ homeostasis. Methods. To explore its physiological functions in the tubular cells, we investigated the effect of SMP30 on Ca 2ϩ efflux via the ATP-dependent plasma membrane calcium pump. LLC-PK1 cells were stably transfected with a cDNA encoding SMP30, and the established transfectants were subjected to ATP responses. Results. Overexpression of SMP30 significantly increased Ca 2ϩ efflux under both basal and ATP-stimulated conditions. Inhibition of calmodulin by trifluoperazine abrogated the enhanced Ca 2ϩ efflux, suggesting that SMP30 activated the calmodulin-dependent Ca 2ϩ pump. It is known that Ca 2ϩ superfluous influx induces cellular injury. Compared with mock-transfected cells, LLC-PK1 cells expressing SMP30 showed resistance to cellular death triggered by Ca 2ϩ superfluous influx. Conclusion. These results suggest the possibility that, in renal tubular cells, endogenous SMP30 participates in Ca 2ϩ efflux via activating the calmodulin-dependent Ca 2ϩ pump and thereby confers resistance of the cells against injury caused by high intracellular Ca 2ϩ concentrations.
To investigate whether human endogenous retroviruses (HERV) contribute to autoimmune diseases, we prepared a recombinant p30gag protein derived from clone 4-1 of the HERV family, using a baculovirus-vector system. This p30gag protein (CA41B) was approximately 30 kDa, as expected, and reacted with antibodies for p30gag purified from both murine and feline leukemia virus. This result suggested that the antigenic determinant for p30gag was well conserved in CA41B. Analysis of serum antibodies to p30gag in patients with autoimmune diseases was done by Western blotting. CA41B detected anti-p30gag antibodies in 48.3% of systemic lupus erythematosus (SLE) patients, 35.0% of Sjögren's syndrome (SS) patients, and 33.3% of mixed connective tissue disease (MCTD) patients, whereas no anti-p30gag antibodies were found in healthy subjects. This suggested that HERV p30gag or other retroviral p30gag proteins possessing the same antigenic determinant as CA41B may play a role in these diseases. Although detection of antibodies to HERV p30gag in autoimmune diseases is indirect evidence that HERV proteins are involved, this study showed that patients with autoimmune diseases have antibodies to HERV p30gag using a recombinant HERV protein rather than synthetic peptides based on HERV or retroviral proteins of other species.
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