Endogenous And Exogenous Connective Tissue Growth Factor, Differentiation And Collagen Synthesis In Vitro Studies Of The Effects Of Human Renal Tubular Epithelial Cells

Tubulointerstitial fibrosis(TIF), a common finding in patients with progressive chronic renal disease of all types, arises because of a complex interplay between factors in the tubular lumen, tubular epithelial cells, peritubular capillaries, resident and infiltrating interstitial cells and extracellular matrix(ECM). Several factors: macrophages, growth factors, hypoxia, cytokines are involved in the pathogenesis of TIF. All these changes result in excessive matrix deposition that leads to tissue destruction and impairment of renal function. It is evident that the process of renal fibrosis is a complicated one with several cellular and molecular mediators interacting in concert, and transforming growth factor-β₁(TGF-β₁) plays an important role among them. TGF-β₁ increases deposition of ECM, resulting in TIF through multi-pathways. The use of anti- TGFβ₁ antibody and TGFβ₁ antisense oligonucleotide(ODN) can both alleviate the extent of TIF, but long inhibition of TGF-β₁ function will result in serious inflammation and cancers. Therefore, more specific targets of antifibrotic therapy are needed that leave TGFβ₁'s positive effects unhindered, while blocking its profibrotic effects.Connective tissue growth factor(CTGF) has been demonstrated the downriver cytokine of TGF-β₁ by multi-researches. In comparison with that found in the normal kidney, CTGF expression is markedly elevated in kinds of nephronia. Increased expression of CTGF correlates with the increased expression level of TGF-β₁. Considerable attention has been directed toward the TGF-Pi induction of CTGF expression, which is rapid and occurs within 30 min of TGF-β₁ stimulation and in the absence of de-novo protein synthesis. Later researches provided the proof: the CTGF promoter contains a TGF-β₁ response element (TbRE/BCE-1) and a Smad-binding element which confer this induction. Cell level researches...