{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:56:58Z","timestamp":1791284218620,"version":"4.1.0"},"reference-count":19,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["20K08599"],"award-info":[{"award-number":["20K08599"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Transforming growth factor-\u03b21 (TGF-\u03b21) is a key profibrotic mediator in diabetic kidney disease. Upstream stimulatory factor 1 (USF1) enhances TGF-\u03b21 transcription through an E-box\/glucose-response element in the TGF-\u03b21 promoter under high-glucose conditions. We designed a sequence-specific pyrrole-imidazole (PI) polyamide targeting the human USF1-binding site in the TGF-\u03b21 promoter and evaluated its activity in human renal mesangial cells (HRMCs). A target PI polyamide and a mismatch PI polyamide were synthesized. DNA binding and inhibition of the USF1\u2013DNA interaction were assessed by gel mobility shift assays. HRMCs were exposed to high glucose with or without PI polyamides, and TGF-\u03b21 and osteopontin expression were quantified by real-time PCR and Western blotting. The target PI polyamide bound the intended promoter sequence and reduced recombinant USF1 binding in vitro. In high-glucose-exposed HRMCs, the target PI polyamide suppressed TGF-\u03b21 mRNA and protein expression, whereas the mismatch PI polyamide did not suppress TGF-\u03b21 expression. The target PI polyamide also reduced osteopontin mRNA expression. These findings provide proof-of-concept that PI polyamide-mediated targeting of the human USF1\u2013TGF-\u03b21 axis can attenuate high-glucose-associated profibrotic responses in HRMCs.<\/jats:p>","DOI":"10.3390\/cells15191818","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:46:29Z","timestamp":1791283589000},"page":"1818","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Pyrrole-Imidazole Polyamide Targeting Human USF1 Binding Suppresses High Glucose-Induced TGF-\u03b21 and Osteopontin Expression in Human Renal Mesangial Cells"],"prefix":"10.3390","volume":"15","author":[{"given":"Yurie","family":"Akiya","sequence":"first","affiliation":[{"name":"Division of Nephrology, Hypertension, and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-chou, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9674-0374","authenticated-orcid":false,"given":"Hiroki","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Hypertension, and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-chou, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Akiko","family":"Tsunemi","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Hypertension, and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-chou, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Noboru","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology, Ukima Chuo Hospital, Tokyo 115-0052, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9156-5415","authenticated-orcid":false,"given":"Masanori","family":"Abe","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Hypertension, and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-chou, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"ref_1","first-page":"901","article-title":"Differential role of mesangial cells and podocytes in TGF-beta-induced mesangial matrix synthesis in chronic glomerular disease","volume":"24","author":"Lee","year":"2009","journal-title":"Histol. 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