Molecular biological analysis of GBM injury in glomerulonephritis

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The genomic mutation in type IV collagen in patients with glomerular basement membrane (GBM) injuryAlport syndrome (AS) is congenital glomerulonephritis characterized by the duplication or splitting of GBM and the responsible gene for AS has been identified as alpha chain of type IV collagen (alpha(IV)). However, the relationship between the gene abnormalities and various phenotypes remains unknown. Recently, it has been reported that patients with AS caused by deletions spanning the alpha5 (IV) (COL4A5) to alpha6( IV) chaingenes (COL4A6) are complicated by esophageal smooth muscle tumor. We havebeen analyzing a gene mutation in a male AS patient complicated with mental retardation but not with esophageal smooth muscle tumor. We had found that he had a complete deletion of the COL4A5 which may involve the junction between COL4A5 and COL4A6. In the last year, we have further investigated the extent of the deletion toward COL4A6 using polymerase chain reaction and found that COL4A6 was a … More lso completely deleted. It is thus speculated that, the esophageal smooth muscle tumoris not caused by a complete deletion of both COL4A5 and COL4A6 but may result from expression of mulfunctonal type IV collagen proteins.Glomerulonephritis and GBM injury in rat experimental modelIn anti-Thy 1 (ATS) nephritis, mesangiolysis followed by mesangial cell proliferation occurs transiently by single injection of ATS,while the twice injections of ATS induce progressiveglomerulosclerosis and GBM injury. Although various cytokines and growth factors are known to participate in these pathological processes, little is known about the mechanisms which regulate expression of these factors in glomeruli. To gain insight into the mechanisms, we examined the activation of transcription factor AP-1 and NF-kB in glomeruli in ATS nephritis model. We foundthat of the transcription factors were activated at the stage of mesangial cell proliferation. We also obtained the evidence of glomerular expression of inducible nitric oxide synthase which may play a role in mesangial and GBM injuries. Less