Proteinuria predicts the decline of renal function in chronic kidney disease. Reducing albuminuria has been shown to be associated with a reduction in this rate of decline. Proximal tubular epithelial cells (PTECs), when exposed to albumin produce matrix proteins, proinflammatory and profibrotic cytokines like TGF-beta(1). Some of these effects are dependent on endocytosis of albumin by PTECs. However, conditions like diabetic nephropathy, believed to be associated with reduced albumin endocytosis, are associated with interstitial fibrosis. Moreover, megalin, the putative albumin binding receptor in PTECs, has potential signaling motifs in its cytoplasmic domain, suggesting its ability to signal in response to ligand binding from the apical surface of PTECs. Hence, we looked to see whether albumin-induced secretion of TGF-beta(1) by PTECs is dependent on albumin endocytosis or whether it could occur in the absence of albumin endocytosis. We studied the production of TGF-beta(1) in two accepted models of PTECs, opossum kidney cells and human kidney cell clone-8 cells, with widely varying degrees of endocytosis. We then studied the effect of inhibiting albumin endocytosis with various inhibitors on albumin-induced TGF-beta(1) secretion. Our results indicate that albumin-induced TGF-beta(1) secretion by PTECs does not require albumin endocytosis and therefore the mechanism for the induction of some profibrotic responses by albumin may differ from those required for some of the inflammatory responses. Moreover, we found that albumin-induced TGF-beta(1) secretion by PTECs is not dependent on its interaction with megalin.

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Background: Pasteurella multocida is an important bacterial pathogen that causes many major diseases of which haemorrhagic septiciemia (HS) in cattle and buffalo is responsible for catastrophic epizootics in India and South Asia. In India, the disease haemorrhagic septiciemia is considered as the most dreaded bacterial disease. Various host- and pathogen- specific determinants are responsible for disease outcome. Various bacterial virulence genes (tbpA, pfhA, toxA, hgbB, hgbA, nanH, nanB, sodA, sodC, oma87 and ptfA) have been proposed to play a key role in this interaction. Methods: The present study was done to compare the gene and deduced amino acid sequence of transferrin binding protein gene (tbpA) gene of field isolates and vaccine strain of P. multocida B: 2. Result: It was observed that tbpA gene of field and vaccine strains have similar nucleotide sequence except at positions 574 and 620. The sequence of tbpA gene was used for prediction of matured TbpA protein characteristics. The deduced amino acid sequences of 242 amino acids revealed 99% homology with TbpA of P. multocida and with a variety of other TonB-dependent receptor proteins, indicating that it belongs to the family of outer membrane receptors. Deduced amino acid sequence was found to be similar in field and vaccine strains except at 207th amino acid. In field isolates Leucine was there while in vaccine strain Phenyl alanine was found. These both amino acids are hydrophobic in nature so no change in physico-chemical property of TbpA is expected. From this study it is concluded that single amino acid difference between field isolate and vaccine strain might not cause change in its binding and physico-chemical property.