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Contribution of TGF-β1 and Effects of Gene Silencer Pyrrole-Imidazole Polyamides Targeting TGF-β1 in Diabetic Nephropathy

TGF-β1 has been known to induce diabetic nephropathy with renal fibrosis and glomerulosclerosis. DNA-recognized peptide compound pyrrole-imidazole (PI) polyamides as novel biomedicines can strongly bind promoter lesions of target genes to inhibit its transcription. We have developed PI polyamide tar...

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Autores principales: Horikoshi, Shu, Fukuda, Noboru, Tsunemi, Akiko, Okamura, Makiyo, Otsuki, Masari, Endo, Morito, Abe, Masanori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070568/
https://www.ncbi.nlm.nih.gov/pubmed/32093382
http://dx.doi.org/10.3390/molecules25040950
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author Horikoshi, Shu
Fukuda, Noboru
Tsunemi, Akiko
Okamura, Makiyo
Otsuki, Masari
Endo, Morito
Abe, Masanori
author_facet Horikoshi, Shu
Fukuda, Noboru
Tsunemi, Akiko
Okamura, Makiyo
Otsuki, Masari
Endo, Morito
Abe, Masanori
author_sort Horikoshi, Shu
collection PubMed
description TGF-β1 has been known to induce diabetic nephropathy with renal fibrosis and glomerulosclerosis. DNA-recognized peptide compound pyrrole-imidazole (PI) polyamides as novel biomedicines can strongly bind promoter lesions of target genes to inhibit its transcription. We have developed PI polyamide targeting TGF-β1 for progressive renal diseases. In the present study, we evaluated the contribution of TGF-β1 in the pathogenesis of diabetic nephropathy, and examined the effects of PI polyamide targeting TGF-β1 on the progression of diabetic nephropathy in rats. For in vitro experiments, rat renal mesangial cells were incubated with a high (25 mM) glucose concentration. Diabetic nephropathy was established in vivo in eight-week-old Wistar rats by intravenously administering 60 mg/kg streptozotocin (STZ). We examined the effects of PI polyamide targeting TGF-β1 on phenotype and the growth of mesangial cells, in vitro, and the pathogenesis of diabetic nephropathy in vivo. High glucose significantly increased expression of TGF-β1 mRNA, changed the phenotype to synthetic, and increased growth of mesangial cells. STZ diabetic rats showed increases in urinary excretions of protein and albumin, glomerular and interstitial degenerations, and podocyte injury. Treatment with PI polyamide targeting TGF-β1 twice weekly for three months improved the glomerular and interstitial degenerations by histological evaluation. Treatment with PI polyamide improved podocyte injury by electron microscopy evaluation. These findings suggest that TGF-β1 may be a pivotal factor in the progression of diabetic nephropathy, and PI polyamide targeting TGF-β1 as a practical medicine may improve nephropathy.
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spelling pubmed-70705682020-03-19 Contribution of TGF-β1 and Effects of Gene Silencer Pyrrole-Imidazole Polyamides Targeting TGF-β1 in Diabetic Nephropathy Horikoshi, Shu Fukuda, Noboru Tsunemi, Akiko Okamura, Makiyo Otsuki, Masari Endo, Morito Abe, Masanori Molecules Article TGF-β1 has been known to induce diabetic nephropathy with renal fibrosis and glomerulosclerosis. DNA-recognized peptide compound pyrrole-imidazole (PI) polyamides as novel biomedicines can strongly bind promoter lesions of target genes to inhibit its transcription. We have developed PI polyamide targeting TGF-β1 for progressive renal diseases. In the present study, we evaluated the contribution of TGF-β1 in the pathogenesis of diabetic nephropathy, and examined the effects of PI polyamide targeting TGF-β1 on the progression of diabetic nephropathy in rats. For in vitro experiments, rat renal mesangial cells were incubated with a high (25 mM) glucose concentration. Diabetic nephropathy was established in vivo in eight-week-old Wistar rats by intravenously administering 60 mg/kg streptozotocin (STZ). We examined the effects of PI polyamide targeting TGF-β1 on phenotype and the growth of mesangial cells, in vitro, and the pathogenesis of diabetic nephropathy in vivo. High glucose significantly increased expression of TGF-β1 mRNA, changed the phenotype to synthetic, and increased growth of mesangial cells. STZ diabetic rats showed increases in urinary excretions of protein and albumin, glomerular and interstitial degenerations, and podocyte injury. Treatment with PI polyamide targeting TGF-β1 twice weekly for three months improved the glomerular and interstitial degenerations by histological evaluation. Treatment with PI polyamide improved podocyte injury by electron microscopy evaluation. These findings suggest that TGF-β1 may be a pivotal factor in the progression of diabetic nephropathy, and PI polyamide targeting TGF-β1 as a practical medicine may improve nephropathy. MDPI 2020-02-20 /pmc/articles/PMC7070568/ /pubmed/32093382 http://dx.doi.org/10.3390/molecules25040950 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Horikoshi, Shu
Fukuda, Noboru
Tsunemi, Akiko
Okamura, Makiyo
Otsuki, Masari
Endo, Morito
Abe, Masanori
Contribution of TGF-β1 and Effects of Gene Silencer Pyrrole-Imidazole Polyamides Targeting TGF-β1 in Diabetic Nephropathy
title Contribution of TGF-β1 and Effects of Gene Silencer Pyrrole-Imidazole Polyamides Targeting TGF-β1 in Diabetic Nephropathy
title_full Contribution of TGF-β1 and Effects of Gene Silencer Pyrrole-Imidazole Polyamides Targeting TGF-β1 in Diabetic Nephropathy
title_fullStr Contribution of TGF-β1 and Effects of Gene Silencer Pyrrole-Imidazole Polyamides Targeting TGF-β1 in Diabetic Nephropathy
title_full_unstemmed Contribution of TGF-β1 and Effects of Gene Silencer Pyrrole-Imidazole Polyamides Targeting TGF-β1 in Diabetic Nephropathy
title_short Contribution of TGF-β1 and Effects of Gene Silencer Pyrrole-Imidazole Polyamides Targeting TGF-β1 in Diabetic Nephropathy
title_sort contribution of tgf-β1 and effects of gene silencer pyrrole-imidazole polyamides targeting tgf-β1 in diabetic nephropathy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070568/
https://www.ncbi.nlm.nih.gov/pubmed/32093382
http://dx.doi.org/10.3390/molecules25040950
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