Tags

Type your tag names separated by a space and hit enter

N-acetyl-seryl-aspartyl-lysyl-proline ameliorates the progression of renal dysfunction and fibrosis in WKY rats with established anti-glomerular basement membrane nephritis.
J Am Soc Nephrol. 2006 Mar; 17(3):674-85.JA

Abstract

N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), which is hydrolyzed by angiotensin-converting enzyme, is a natural regulator of hematopoiesis. Here it is shown that Ac-SDKP inhibits TGF-beta action in mesangial cells. Because TGF-beta is thought to play a pivotal role in the development and progression of glomerulonephritis, the therapeutic effects of Ac-SDKP on an established model of renal dysfunction and histologic alteration in Wistar-Kyoto rats with anti-glomerular basement membrane nephritis was examined. Fourteen days after the induction of anti-glomerular basement membrane nephritis, the rats were treated subcutaneously with Ac-SDKP at a dose of 1 mg/kg per d for 4 wk. Treatment with Ac-SDKP significantly improved proteinuria and renal dysfunction, including increased plasma blood urea nitrogen and creatinine levels and decreased creatinine clearance. Histologic examination showed severe glomerulosclerosis and interstitial fibrosis in the vehicle-treated rats, whereas these histologic injuries were significantly ameliorated in rats that were treated with Ac-SDKP. The histologic improvements were accompanied by the suppression of gene and protein expression of fibronectin, interstitial collagen, and TGF-beta1 in the nephritic kidney. Furthermore, treatment with Ac-SDKP resulted in the inhibition of Smad2 phosphorylation, an increase in Smad7 expression in the kidney, and reduction of macrophage accumulation into the glomeruli and tubulointerstitium in nephritic rats. In conclusion, Ac-SDKP significantly ameliorated the progression of renal dysfunction and fibrosis even after the establishment of nephritis. The inhibitory effect of Ac-SDKP was mediated in part by the inhibition of TGF-beta/Smad signal transduction and the inflammatory response. These findings suggest that Ac-SDKP treatment may be a novel and useful therapeutic strategy for the treatment of progressive renal diseases.

Authors+Show Affiliations

Biomedical Research Laboratories, Daiichi Asubio Pharma Co., Ltd., 1-1-1 Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-8513, Japan. mitsugu_omata@asubio.co.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

16452498

Citation

Omata, Mitsugu, et al. "N-acetyl-seryl-aspartyl-lysyl-proline Ameliorates the Progression of Renal Dysfunction and Fibrosis in WKY Rats With Established Anti-glomerular Basement Membrane Nephritis." Journal of the American Society of Nephrology : JASN, vol. 17, no. 3, 2006, pp. 674-85.
Omata M, Taniguchi H, Koya D, et al. N-acetyl-seryl-aspartyl-lysyl-proline ameliorates the progression of renal dysfunction and fibrosis in WKY rats with established anti-glomerular basement membrane nephritis. J Am Soc Nephrol. 2006;17(3):674-85.
Omata, M., Taniguchi, H., Koya, D., Kanasaki, K., Sho, R., Kato, Y., Kojima, R., Haneda, M., & Inomata, N. (2006). N-acetyl-seryl-aspartyl-lysyl-proline ameliorates the progression of renal dysfunction and fibrosis in WKY rats with established anti-glomerular basement membrane nephritis. Journal of the American Society of Nephrology : JASN, 17(3), 674-85.
Omata M, et al. N-acetyl-seryl-aspartyl-lysyl-proline Ameliorates the Progression of Renal Dysfunction and Fibrosis in WKY Rats With Established Anti-glomerular Basement Membrane Nephritis. J Am Soc Nephrol. 2006;17(3):674-85. PubMed PMID: 16452498.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - N-acetyl-seryl-aspartyl-lysyl-proline ameliorates the progression of renal dysfunction and fibrosis in WKY rats with established anti-glomerular basement membrane nephritis. AU - Omata,Mitsugu, AU - Taniguchi,Hajime, AU - Koya,Daisuke, AU - Kanasaki,Keizo, AU - Sho,Rumiko, AU - Kato,Yoshimi, AU - Kojima,Ryoji, AU - Haneda,Masakazu, AU - Inomata,Norio, Y1 - 2006/02/01/ PY - 2006/2/3/pubmed PY - 2006/7/28/medline PY - 2006/2/3/entrez SP - 674 EP - 85 JF - Journal of the American Society of Nephrology : JASN JO - J. Am. Soc. Nephrol. VL - 17 IS - 3 N2 - N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), which is hydrolyzed by angiotensin-converting enzyme, is a natural regulator of hematopoiesis. Here it is shown that Ac-SDKP inhibits TGF-beta action in mesangial cells. Because TGF-beta is thought to play a pivotal role in the development and progression of glomerulonephritis, the therapeutic effects of Ac-SDKP on an established model of renal dysfunction and histologic alteration in Wistar-Kyoto rats with anti-glomerular basement membrane nephritis was examined. Fourteen days after the induction of anti-glomerular basement membrane nephritis, the rats were treated subcutaneously with Ac-SDKP at a dose of 1 mg/kg per d for 4 wk. Treatment with Ac-SDKP significantly improved proteinuria and renal dysfunction, including increased plasma blood urea nitrogen and creatinine levels and decreased creatinine clearance. Histologic examination showed severe glomerulosclerosis and interstitial fibrosis in the vehicle-treated rats, whereas these histologic injuries were significantly ameliorated in rats that were treated with Ac-SDKP. The histologic improvements were accompanied by the suppression of gene and protein expression of fibronectin, interstitial collagen, and TGF-beta1 in the nephritic kidney. Furthermore, treatment with Ac-SDKP resulted in the inhibition of Smad2 phosphorylation, an increase in Smad7 expression in the kidney, and reduction of macrophage accumulation into the glomeruli and tubulointerstitium in nephritic rats. In conclusion, Ac-SDKP significantly ameliorated the progression of renal dysfunction and fibrosis even after the establishment of nephritis. The inhibitory effect of Ac-SDKP was mediated in part by the inhibition of TGF-beta/Smad signal transduction and the inflammatory response. These findings suggest that Ac-SDKP treatment may be a novel and useful therapeutic strategy for the treatment of progressive renal diseases. SN - 1046-6673 UR - https://www.unboundmedicine.com/medline/citation/16452498/N_acetyl_seryl_aspartyl_lysyl_proline_ameliorates_the_progression_of_renal_dysfunction_and_fibrosis_in_WKY_rats_with_established_anti_glomerular_basement_membrane_nephritis_ L2 - http://jasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=16452498 DB - PRIME DP - Unbound Medicine ER -