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Indoxyl sulfate increases the gene expressions of TGF-beta 1, TIMP-1 and pro-alpha 1(I) collagen in uremic rat kidneys.
Kidney Int Suppl. 1997 Nov; 62:S15-22.KI

Abstract

We recently reported that the serum levels of indoxyl sulfate, a dietary protein metabolite, are increased in both uremic rats and patients, and that the administration of indoxyl sulfate to uremic rats accelerates the progression of glomerular sclerosis. Thus, we hypothesize that the overload of protein metabolites such as indoxyl sulfate on nephrons promotes the progression of chronic renal failure (CRF). Recent studies revealed that tubulointerstitial injury is of equal or greater importance than glomerular sclerosis in determining whether progressive renal dysfunction will ensue in various renal diseases. In the present study, to clarify the role of indoxyl sulfate in the progression of CRF, the expressions of genes related to tubulointerstitial fibrosis such as transforming growth factor (TGF)-beta 1, tissue inhibitor of metalloproteinases (TIMP-1) and pro-alpha 1(I) collagen were examined in the renal cortex of 5/6-nephrectomized uremic rats given indoxyl sulfate. In the first experiment, the administration of indoxyl sulfate for five weeks significantly increased the mRNA levels of TGF-beta 1, TIMP-1 and pro-alpha 1(I) collagen in the uremic rats given indoxyl sulfate compared with the control uremic rats, accompanied by a significant decline in renal function and worsening of glomerular sclerosis. In the second experiment, the administration of indoxyl sulfate for 2.5 weeks also increased the expression of the mRNA levels with no significant decline in the renal function. In conclusion, these findings indicate that the overload of the protein metabolite indoxyl sulfate on remnant nephrons is involved in the increased bioactivity of TGF-beta 1 in uremic kidneys, which enhances the renal expression of TIMP-1 and type 1 collagen, leading to the progression of CRF.

Authors+Show Affiliations

Nagoya University Daiko Medical Center, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9350672

Citation

Miyazaki, T, et al. "Indoxyl Sulfate Increases the Gene Expressions of TGF-beta 1, TIMP-1 and Pro-alpha 1(I) Collagen in Uremic Rat Kidneys." Kidney International. Supplement, vol. 62, 1997, pp. S15-22.
Miyazaki T, Ise M, Seo H, et al. Indoxyl sulfate increases the gene expressions of TGF-beta 1, TIMP-1 and pro-alpha 1(I) collagen in uremic rat kidneys. Kidney Int Suppl. 1997;62:S15-22.
Miyazaki, T., Ise, M., Seo, H., & Niwa, T. (1997). Indoxyl sulfate increases the gene expressions of TGF-beta 1, TIMP-1 and pro-alpha 1(I) collagen in uremic rat kidneys. Kidney International. Supplement, 62, S15-22.
Miyazaki T, et al. Indoxyl Sulfate Increases the Gene Expressions of TGF-beta 1, TIMP-1 and Pro-alpha 1(I) Collagen in Uremic Rat Kidneys. Kidney Int Suppl. 1997;62:S15-22. PubMed PMID: 9350672.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Indoxyl sulfate increases the gene expressions of TGF-beta 1, TIMP-1 and pro-alpha 1(I) collagen in uremic rat kidneys. AU - Miyazaki,T, AU - Ise,M, AU - Seo,H, AU - Niwa,T, PY - 1997/11/14/pubmed PY - 1997/11/14/medline PY - 1997/11/14/entrez SP - S15 EP - 22 JF - Kidney international. Supplement JO - Kidney Int. Suppl. VL - 62 N2 - We recently reported that the serum levels of indoxyl sulfate, a dietary protein metabolite, are increased in both uremic rats and patients, and that the administration of indoxyl sulfate to uremic rats accelerates the progression of glomerular sclerosis. Thus, we hypothesize that the overload of protein metabolites such as indoxyl sulfate on nephrons promotes the progression of chronic renal failure (CRF). Recent studies revealed that tubulointerstitial injury is of equal or greater importance than glomerular sclerosis in determining whether progressive renal dysfunction will ensue in various renal diseases. In the present study, to clarify the role of indoxyl sulfate in the progression of CRF, the expressions of genes related to tubulointerstitial fibrosis such as transforming growth factor (TGF)-beta 1, tissue inhibitor of metalloproteinases (TIMP-1) and pro-alpha 1(I) collagen were examined in the renal cortex of 5/6-nephrectomized uremic rats given indoxyl sulfate. In the first experiment, the administration of indoxyl sulfate for five weeks significantly increased the mRNA levels of TGF-beta 1, TIMP-1 and pro-alpha 1(I) collagen in the uremic rats given indoxyl sulfate compared with the control uremic rats, accompanied by a significant decline in renal function and worsening of glomerular sclerosis. In the second experiment, the administration of indoxyl sulfate for 2.5 weeks also increased the expression of the mRNA levels with no significant decline in the renal function. In conclusion, these findings indicate that the overload of the protein metabolite indoxyl sulfate on remnant nephrons is involved in the increased bioactivity of TGF-beta 1 in uremic kidneys, which enhances the renal expression of TIMP-1 and type 1 collagen, leading to the progression of CRF. SN - 0098-6577 UR - https://www.unboundmedicine.com/medline/citation/9350672/Indoxyl_sulfate_increases_the_gene_expressions_of_TGF_beta_1_TIMP_1_and_pro_alpha_1_I__collagen_in_uremic_rat_kidneys_ DB - PRIME DP - Unbound Medicine ER -