Research on The Role of Proximal Tubular Cells in The Development of Tubulointerstitinal Injury.

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This project was performed to investigate the roles of proximal tubular cells (PTCs) in the promotion of tubulointerstitial inflammation and fibrosis. PTCs produced increased amount of connective tissue growth factor (CTGF) under high concentration of glucose. This phenomenon was partially mediated by TGF-β, but TGF-β independent pathway was also working, PTCs were activated by the bacterial lipopolysaccharide (LPS) resulting in production of chemokines such as MCP-1 and RANTES. This is mediated by toll-like receptor 4 (TLR4). Intracellular signaling pathways of MCP-1 and RANTES production was different, i.e., JNK or NF-κ B for MCP-1 while p38 for RANTES. In the in vivo experiment, gene transfer of mutated MCP-1 gene into rat kidney interstitial cells by retrograde injection via renal vein successfully inhibited tubulointerstitial injury induced by the protein overload nephropathy. From these data, it is suggested that PTCs or interstitial cells can be the target of therapy.