PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Preclinical Study of DNA-Recognized Peptide Pyrrole-Imidazole Polyamide Targeting Human TGF-β1 Promoter for Progressive Renal Diseases in Common Marmoset
Version 1
: Received: 3 August 2019 / Approved: 7 August 2019 / Online: 7 August 2019 (09:42:06 CEST)
How to cite:
Otsuki, M.; Fukuda, N.; Inoue, T.; Mineshige, T.; Otsuki, T.; Horikoshi, S.; Endo, M.; Abe, M. Preclinical Study of DNA-Recognized Peptide Pyrrole-Imidazole Polyamide Targeting Human TGF-β1 Promoter for Progressive Renal Diseases in Common Marmoset. Preprints2019, 2019080090. https://doi.org/10.20944/preprints201908.0090.v1
Otsuki, M.; Fukuda, N.; Inoue, T.; Mineshige, T.; Otsuki, T.; Horikoshi, S.; Endo, M.; Abe, M. Preclinical Study of DNA-Recognized Peptide Pyrrole-Imidazole Polyamide Targeting Human TGF-β1 Promoter for Progressive Renal Diseases in Common Marmoset. Preprints 2019, 2019080090. https://doi.org/10.20944/preprints201908.0090.v1
Otsuki, M.; Fukuda, N.; Inoue, T.; Mineshige, T.; Otsuki, T.; Horikoshi, S.; Endo, M.; Abe, M. Preclinical Study of DNA-Recognized Peptide Pyrrole-Imidazole Polyamide Targeting Human TGF-β1 Promoter for Progressive Renal Diseases in Common Marmoset. Preprints2019, 2019080090. https://doi.org/10.20944/preprints201908.0090.v1
APA Style
Otsuki, M., Fukuda, N., Inoue, T., Mineshige, T., Otsuki, T., Horikoshi, S., Endo, M., & Abe, M. (2019). Preclinical Study of DNA-Recognized Peptide Pyrrole-Imidazole Polyamide Targeting Human TGF-β1 Promoter for Progressive Renal Diseases in Common Marmoset. Preprints. https://doi.org/10.20944/preprints201908.0090.v1
Chicago/Turabian Style
Otsuki, M., Morito Endo and Masanori Abe. 2019 "Preclinical Study of DNA-Recognized Peptide Pyrrole-Imidazole Polyamide Targeting Human TGF-β1 Promoter for Progressive Renal Diseases in Common Marmoset" Preprints. https://doi.org/10.20944/preprints201908.0090.v1
Abstract
Pyrrole-imidazole (PI) polyamides are novel gene silencers that strongly bind the promoter region of target genes in a sequence-specific manner to inhibit gene transcription. We developed a PI polyamide targeting human TGF-b1 (hTGF-b1). To develop PI polyamide targeting hTGF-b1 (Polyamide) as a practical medicine for progressive renal diseases, we examined the effects of Polyamide in two common marmoset models of nephropathy.We performed lead optimization of PI polyamides targeting hTGF-b1 by the dose-dependent inhibition of the PMA-stimulated expression of TGF-b1 mRNA in marmoset fibroblasts. Marmosets were housed with a 0.05% NaCl and magnesium diet and treated with cyclosporine A (CsA; 37.5 mg/kg/day, 8 weeks) to establish chronic nephropathy. Marmosets with nephropathy were treated with Polyamide (1 mg/kg/week, 4 weeks). We also established a unilateral urethral obstruction(UUO) model and examined the effects of Polyamide (1 mg/kg/week, 4 times) in marmosets.Histologically, the renal medulla from CsA-treated marmosets showed cast formation and interstitial fibrosis in the renal medulla. Immunohistochemistry showed strong staining of Polyamide in the renal medulla from CsA-treated marmosets.Polyamidetreatment (1 mg/kg/week, 4 times) reduced hTGF-b1 staining and urinary protein excretion in CsA-treated marmosets. Polyamide reduced the glomerular injury score (GIS) and tubulointerstitial injury score (TIS) in UUO kidneys from marmosets. Polyamide significantly suppressed the hTGF-b1 and Snail mRNA expressionin UUO kidneys from marmosets.PI polyamide effectively improved CsA- and UUO-associated nephropathy, indicating its potential application in the prevention of renal fibrosis in progressive renal diseases.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
