Smad3 deficiency attenuates renal fibrosis, inflammation,and apoptosis after unilateral ureteral obstruction

Abstract

Fibrosis of the tubulointerstitial compartment often accompanied by inflammation is a major factor in progressive loss of renal function in patients with a variety of kidney diseases¹ x 1. Klahr, S., Schreiner, G., and Ichicawa, I. The progression of renal disease. N Engl J Med. 1988; 318: 1657–1666 Crossref | PubMed | Scopus (681) | Google Scholar See all References ^,2 x 2. Eddy, A.A. Molecular insight into renal interstitial fibrosis. J Am Soc Nephrol. 1996; 7: 2495–2508 PubMed | Google Scholar See all References . Unilateral ureteral obstruction (UUO) is a representative model of tubulointerstitial renal fibrosis that have many readily quantifiable cellular and molecular events during the initiation and progression of renal fibrosis such as inflammation and apoptosis³ x 3. Klahr, S. and Morrissey, J. Obstructive nephropathy and renal fibrosis. Am J Physiol Renal Physiol. 2002; 283: F861–F875 Crossref | PubMed | Google Scholar See all References . Although many factors are involved in the pathophysiology of UUO³ x 3. Klahr, S. and Morrissey, J. Obstructive nephropathy and renal fibrosis. Am J Physiol Renal Physiol. 2002; 283: F861–F875 Crossref | PubMed | Google Scholar See all References , it is well accepted that transforming growth factor-β (TGF-β) is a key molecule for the development of tubulointerstitial fibrosis in UUO^3. x 3. Klahr, S. and Morrissey, J. Obstructive nephropathy and renal fibrosis. Am J Physiol Renal Physiol. 2002; 283: F861–F875 Crossref | PubMed | Google Scholar See all References ^{, 4.} x 4. Walton, G., Buttyan, R., Garcia, M.E. et al. Renal growth factor expression during the early phase of experimental hydronephrosis. J Urol. 1992; 148: 510–514 PubMed | Google Scholar See all References ^{, 5.} x 5. Diamond, J.R., Kees, F.D., Ding, G. et al. Macrophages, monocyte chemoattractant peptide-1, and TGF-β1 in experimental hydronephrosis. Am J Physiol Renal Fluid Electrolyte Physiol. 1993; 266: F874–F881 Google Scholar See all References ^{, 6.} x 6. Kaneto, H., Morrissey, J., and Klahr, S. Increased expression of TGF-β1 mRNA in the obstructed kidney of rats with unilateral ureteral ligation. Kidney Int. 1993; 44: 313–321 Abstract | Full Text PDF | PubMed | Scopus (284) | Google Scholar See all References ^{, 7.} x 7. Sutaria, P.M., Ohebshalom, M., Mccaffrey, T.A. et al. Transforming growth factor-β receptor type I and II are expressed in renal tubules and are increased after chronic unilateral ureteral obstruction. Life Sci. 1998; 62: 1965–1972 Crossref | PubMed | Scopus (36) | Google Scholar See all References ^{, 8.} x 8. Miyajima, A., Chen, J., Lawrence, C. et al. Antibody to transforming growth factor-β ameliorates tubular apoptosis in unilateral ureteral obstruction. Kidney Int. 2000; 58: 2301–2313 Abstract | Full Text | Full Text PDF | PubMed | Scopus (254) | Google Scholar See all References ^{, 9.} x 9. Isaka, Y., Tsujie, M., Ando, Y. et al. Transforming growth factor-β1 antisense oligonucleotides block interstitial fibrosis in unilateral ureteral obstruction. Kidney Int. 2000; 58: 1885–1892 Abstract | Full Text | Full Text PDF | PubMed | Scopus (0) | Google Scholar See all References ^{, 10.} x 10. Fukuda, K., Yoshitomi, K., Yanagida, T. et al. Quantification of TGF-β1 mRNA along rat nephron in obstructive nephropathy. Am J Physiol Renal Physiol. 2001; 281: F513–F521 PubMed | Google Scholar See all References . It is generally thought that TGF-β is involved in tissue fibrosis including renal fibrosis induced by UUO based on its capacity to induce extracellular matrix (ECM) production, differentiation from fibroblasts into myofibroblasts, and apoptosis^3. x 3. Klahr, S. and Morrissey, J. Obstructive nephropathy and renal fibrosis. Am J Physiol Renal Physiol. 2002; 283: F861–F875 Crossref | PubMed | Google Scholar See all References ^{, 8.} x 8. Miyajima, A., Chen, J., Lawrence, C. et al. Antibody to transforming growth factor-β ameliorates tubular apoptosis in unilateral ureteral obstruction. Kidney Int. 2000; 58: 2301–2313 Abstract | Full Text | Full Text PDF | PubMed | Scopus (254) | Google Scholar See all References ^{, 11.} x 11. Border, W. and Noble, N. Transforming growth factor-β in tissue fibrosis. N Engl J Med. 1994; 331: 1286–1292...