Evidence mapPaperPMID 39042147Full record

ArticleGraefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie2025

Inhibition of mTOR differently modulates planar and subepithelial fibrogenesis in human conjunctival fibroblasts.

Megumi Watanabe, Yuri Tsugeno, Tatsuya Sato, Megumi Higashide, Araya Umetsu, Masato Furuhashi, Hiroshi Ohguro

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Article in Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Megumi Watanabe *Department of Ophthalmology, Sapporo Medical University School of Medicine, Sapporo Ika Daigaku, Hirosaki, Japan. watanabe@sapmed.ac.jp.
Yuri Tsugeno *Department of Ophthalmology, Sapporo Medical University School of Medicine, Sapporo Ika Daigaku, Hirosaki, Japan.
Tatsuya Sato *Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo Ika Daigaku, Hirosaki, Japan.
Megumi HigashideDepartment of Ophthalmology, Sapporo Medical University School of Medicine, Sapporo Ika Daigaku, Hirosaki, Japan.
Araya UmetsuDepartment of Ophthalmology, Sapporo Medical University School of Medicine, Sapporo Ika Daigaku, Hirosaki, Japan.
Masato FuruhashiCardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo Ika Daigaku, Hirosaki, Japan.
Hiroshi OhguroDepartment of Ophthalmology, Sapporo Medical University School of Medicine, Sapporo Ika Daigaku, Hirosaki, Japan. ooguro@sapmed.ac.jp.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeIn the current investigation, the effects of the mTOR inhibitors, Rapa and Torin1 on the TGF-β2-induced conjunctival fibrogenesis were studied. STUDY

designExperimental research.

methods2D and 3D cultures of HconF were subjected to the following analyses; (1) planar proliferation evaluated by TEER (2D), (2) Seahorse metabolic analyses (2D), (3) subepithelial proliferation evaluated by the 3D spheroids' size and hardness, and (4) the mRNA expression of ECM proteins and their regulators (2D and 3D).

resultRapa or Torin1 both significantly increased planar proliferation in the non-TGF-β2-treated 2D HconF cells, but in the TGF-β2-treated cells, this proliferation was inhibited by Rapa and enhanced by Torin1. Although Rapa or Torin1 did not affect cellular metabolism in the non-TGF-β2-treated HconF cells, mTOR inhibitors significantly decreased and increased the mitochondrial respiration and the glycolytic capacity, respectively, under conditions of TGF-β2-induced fibrogenesis. Subepithelial proliferation, as evidenced by the hardness of the 3D spheroids, was markedly down-regulated by both Rapa and Torin1 independent of TGF-β2. The mRNA expressions of several ECM molecules and their regulators fluctuated in the cases of 2D vs 3D and TGF-β2 untreated vs treated cultures.

conclusionThe present findings indicate that mTOR inhibitors have the ability to increase and to reduce planar and subepithelial proliferation in HconF cells, depending on the inhibitor being used.

Indexed as

ConjunctivaFibroblastsMTOR InhibitorsTOR Serine-Threonine KinasesCell ProliferationCells, CulturedFibrosisHumansReal-Time Polymerase Chain ReactionSirolimusMTOR InhibitorsMTOR protein, humanSirolimusTOR Serine-Threonine Kinases3D spheroid cultureHuman conjunctival fibroblastmTOR inhibitorTGF-β2

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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 Socratic graph.