Evidence map›Paper›PMID 37875848›Full record

ArticleBMC urology2023

Distinct effects of Fgf7 and Fgf10 on the terminal differentiation of murine bladder urothelium revealed using an organoid culture system.

Kazuto Suda, Yuka Matsumoto, Takanori Ochi, Hiroyuki Koga, Nobutaka Hattori, Atsuyuki Yamataka, Tetsuya Nakamura

Open access · goldAbstract read
In one paragraph

Article in BMC urology, 2023. 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
0.9field-weighted citation impact, top 24% of its field
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, 3 citations in OpenAlex.

  1. Review
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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

7 authors at 1 institution in 1 country.

Kazuto Suda *Department of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, 2- 1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. kdsuda@juntendo.ac.jp.
Yuka MatsumotoDepartment of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, 2- 1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Takanori OchiDepartment of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, 2- 1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Hiroyuki KogaDepartment of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, 2- 1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Nobutaka HattoriDepartment of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
Atsuyuki YamatakaDepartment of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, 2- 1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Tetsuya Nakamura *Department of Research and Development for Organoids, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. t.nakamura.sv@juntendo.ac.jp.
Juntendo University · JP

Funding

GSK Japan Research Grant 2019 D-17GSK Japan Research Grant 2021 AS2021A000149025Japan Society for the Promotion of Science 19K09083Japan Society for the Promotion of Science 20K21637Juntendo University Project Grant No. 2020-19
6 · The paper itself

Abstract

backgroundDysregulation of the terminal differentiation of bladder urothelium is associated with the pathogenesis of urinary tract disorders. Fibroblast growth factor (Fgf)7 and Fgf10 stimulate urothelial proliferation; however, their roles in cellular differentiation remain unclear. In this study, we used an organoid system to investigate the roles of these Fgfs in regulating bladder urothelium differentiation and identify their distribution patterns in the mouse bladder.

methodsAdult bladder epithelia (AdBE) isolated from adult mouse bladder tissues (AdBTs) were used to culture adult bladder organoids (AdBOs) in the presence of Fgf7 and Fgf10. The differentiation status of the cells in AdBTs, AdBEs, AdBOs, and neonatal bladder tissues (NeoBTs) was analyzed via quantitative real-time-PCR for the presence of undifferentiated cell markers (Krt5, Trp63, and Krt14) and differentiated cell markers (Krt20, Upk1a, Upk2, and Upk3a). Organoid cell proliferation was assessed by counting cell numbers using the trypan blue method. The effects of Fgf7 and Fgf10 on organoid differentiation were assessed using different doses of Fgfs, and the involvement of peroxisome proliferator-activated receptor γ (PPARγ) signaling in these processes was tested by introducing a PPARγ agonist (Rosiglitazone) and antagonist (T0070907) to the culture. The expression patterns of Fgf7 and Fgf10 were examined via in situ hybridization of AdBTs.

resultsAdBOs showed higher expression of undifferentiated cell markers and lower expression of differentiated cell markers than AdBTs, NeoBTs, and AdBEs, indicating the relatively immature state of AdBOs. Differentiation of AdBOs was enhanced by Rosiglitazone and Fgf7, suggesting an interplay of intracellular signals between Fgf7 and PPARγ. Co-addition of T0070907 suppressed Fgf7-mediated differentiation, demonstrating that PPARγ is activated downstream of Fgf7 to promote cellular differentiation into umbrella cells. Furthermore, we found that Fgf7 is predominantly expressed in the umbrella cells of the urothelium, whereas Fgf10 is predominantly expressed in the urothelium and stroma of AdBTs.

conclusionsWe demonstrated that unlike Fgf10, Fgf7 induces cellular differentiation via PPARγ activity and has a unique tissue distribution pattern in the adult bladder. Further studies on the Fgf7-PPARγ signaling axis would provide insights into the differentiation mechanisms toward functional umbrella cells and the pathogenesis of several urinary tract diseases.

Indexed as

PPAR gammaUrinary BladderAnimalsBenzamidesCell DifferentiationFibroblast Growth Factor 10Fibroblast Growth Factor 7MiceOrganoidsPyridinesRosiglitazoneUroplakin IIIUrotheliumBenzamidesFgf10 protein, mouseFgf7 protein, mouseFibroblast Growth Factor 10Fibroblast Growth Factor 7PPAR gammaPyridinesRosiglitazoneT 0070907Upk3a protein, mouseUroplakin IIIBladderDifferentiationFibroblast growth factor 10Fibroblast growth factor 7OrganoidPeroxisome proliferator-activated receptor γUrothelium

Identifiers

PMID37875848
PMCPMC10594814
OpenAlexW4387906037

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.