Evidence map›Paper›PMID 39384357›Full record

ArticleKidney research and clinical practice2025

Evaluation of the novel ALK5 inhibitor EW-7197 on therapeutic efficacy in renal fibrosis using a three-dimensional chip model.

So Young Jang, Seong-Hye Hwang, Yunyeong Choi, Wan-Young Kim, Sung Hyuk Park, Won Mook Kim, Eun-Jeong Kwon, Sejoong Kim

Abstract read
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Article in Kidney research and clinical practice, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

So Young JangDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Seong-Hye HwangDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Yunyeong ChoiDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Wan-Young KimDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Sung Hyuk ParkDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Won Mook KimBiophammer Inc., Pohang, Republic of Korea.
Eun-Jeong KwonDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Sejoong KimDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEW-7197, a potent oral ALK5 inhibitor, was assessed for its impact on transforming growth factor beta 1 (TGF-β1)-induced fibrosis in a three-dimensional (3D) renal fibrosis-on-a-chip and a mouse model. The evaluation included tubular epithelial- mesenchymal transition, angiogenesis, and inflammatory cytokine expression.

methodsIn a 3D renal fibrosis-on-a-chip model, three cell types(kidney fibroblasts, human proximal tubular cells, and human umbilical vein endothelial cells) were cultured and treated with TGF-β1 and EW-7197. Alpha smooth muscle actin (α-SMA) and keratin 8 (KRT-8) was assessed, angiogenesis observed via confocal microscopy, and cytokine levels measured by polymerase chain reaction, immunoassay, and enzyme-linked immunosorbent assay. In a cisplatin-induced renal fibrosis mouse model, blood urea nitrogen levels, TGF-β, and Smad 2/3 were determined, and fibrosis was assessed with Masson's trichrome stain.

resultsThe α-SMA expression was significantly lower in the EW-7197 group than in the TGF-β fibrosis group. TGF-β decreased the expression of the epithelial marker KRT-8, an effect that was reversed by EW-7197 and SB431542. In the TGF-β-induced fibrosis model, the length of the thick vessels was reduced, and the diameter of both thick and thin vessels was decreased, but EW-7197 reversed these effects. EW-7197 significantly reduced the messenger RNA expression of TGF-β and increased the levels of vascular endothelial growth factor receptor 2, interleukin (IL)-10, and IL-6. EW-7197 reduced the levels of secretory cytokines TGF-β1, TGF-β3, IL- 1β. In the cisplatin-induced renal fibrosis mouse model, EW-7197 reduced renal fibrosis by down-regulating TGF-β signaling.

conclusionEW-7197 attenuated the TGF-β1-induced fibrotic cellular response in the 3D chip model and animal model. These findings indicate the potential effect of EW-7197 in attenuating renal fibrosis.

Indexed as

Chronic renal failureFibrosisOrgan-on-a-chipVactosertib

Identifiers

PMID39384357
PMCPMC12245568

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.