Evidence map›Paper›PMID 40968381›Full record

ArticleStem cell research & therapy2025

iPSC-based drug discovery identified the Hippo signaling pathway as a therapeutic target in the fibrosis of NPHP1-deficient nephronophthisis.

Takefumi Suzuki, Koichiro Susa, Hiroaki Kikuchi, Yuta Nakano, Tomoki Yanagi, Yu Hara, Tamami Fujiki, Fumiaki Ando, Shintaro Mandai, Yutaro Mori and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Takefumi SuzukiDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Koichiro SusaDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan. ksusa.kid@tmd.ac.jp.
Hiroaki KikuchiDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Yuta NakanoDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Tomoki YanagiDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Yu HaraDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Tamami FujikiDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Fumiaki AndoDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Shintaro MandaiDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Yutaro MoriDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Takayasu MoriDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Hiroaki IwasaResearch and Development Division, Perseus Proteomics Inc, Tokyo, Japan.
Yutaka HataPreventive Medical Center, Sunkohkai Medical Corp. Koga Community Hospital, Yaizu, Shizuoka, Japan.
Shinichi UchidaDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Eisei SoharaDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan. esohara.kid@tmd.ac.jp.

Funding

Japan Agency for Medical Research and Development 19ek0109304h0002Japan Agency for Medical Research and Development 21ek0109554h0001Japan Agency for Medical Research and Development 24ek0310023h0001Japan Agency for Medical Research and Development JP21ek0310018Japan Society for the Promotion of Science 19H01049Japan Society for the Promotion of Science 19H03672Japan Society for the Promotion of Science 19K17699Japan Society for the Promotion of Science 23K19610
6 · The paper itself

Abstract

backgroundNephronophthisis (NPH) is an autosomal recessive kidney disease, and NPHP1 is the most frequently affected gene. Tubulointerstitial fibrosis is the major phenotype of NPHP1-deficient NPH. The pathophysiology of NPHP1-deficient NPH is unclear because models representing the disease pathophysiology are lacking. Herein, we aimed to create a novel pathological model of NPH using 3D kidney organoids derived from human-induced pluripotent stem cells (iPSCs) and elucidated the pathophysiology while searching for therapeutic candidates.

methodsNPHP1-deficient kidney organoids were generated from iPSCs. Fibrosis was induced by treatment with IL-1β. The effects of the Hippo signaling pathway inhibitors as therapeutic candidates were assessed. Fibrotic status was evaluated using immunofluorescence and quantitative PCR.

resultsNPHP1

conclusionsHippo signaling pathway is involved in the fibrotic changes associated with NPHP1-deficient NPH and the Hippo pathway inhibitors could be therapeutic agents. CLINICAL TRIAL NUMBER: Not applicable.

Indexed as

Adaptor Proteins, Signal TransducingDrug DiscoveryInduced Pluripotent Stem CellsKidney Diseases, CysticProtein Serine-Threonine KinasesCytoskeletal ProteinsFibrosisHippo Signaling PathwayHumansInterleukin-1betaKidneyOrganoidsSignal TransductionAdaptor Proteins, Signal TransducingCytoskeletal ProteinsInterleukin-1betaNPHP1 protein, humanProtein Serine-Threonine KinasesFibrosisHippo signaling pathwayKidney organoidNephronophthisis (NPH)Stem cell

Identifiers

PMID40968381
PMCPMC12447615

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.