Evidence map›Paper›PMID 42536701›Full record

ArticleThe Journal of clinical investigation2026

Branched-chain amino acid transaminase 1-mediated pathway promotes proline-dependent collagen production in cardiac myofibroblasts.

Noburo Takizawa, Takanori Hironaka, Hayato Watanabe, Haruna Suetsugu, Keisuke Yoshioka, Yuma Horii, Yuri Nagata, Hiroaki Matoba, Hidetaka Kosako, Kenji Hamase and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

12 authors.

Noburo TakizawaDepartment of Disease Control, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Takanori HironakaDepartment of Disease Control, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Hayato WatanabeDepartment of Disease Control, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Haruna SuetsuguDepartment of Disease Control, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Keisuke YoshiokaDepartment of Disease Control, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Yuma HoriiDepartment of Disease Control, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Yuri NagataDepartment of Drug Discovery and Evolution, Graduate School of Pharmaceutical Sciences, and.
Hiroaki MatobaDepartment of Pharmaceutical Synthetic Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Hidetaka KosakoDivision of Cell Signaling, Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan.
Kenji HamaseDepartment of Drug Discovery and Evolution, Graduate School of Pharmaceutical Sciences, and.
Go HiraiDepartment of Pharmaceutical Synthetic Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Michio NakayaDepartment of Disease Control, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Myofibroblasts are the cells responsible for collagen production, leading to tissue fibrosis. Because 20.5% of the total amino acids in collagen are proline, myofibroblasts must acquire a well-developed proline-producing mechanism during their differentiation. However, the detailed mechanism for myofibroblasts to acquire and keep the developed proline biosynthesis machinery remains obscure. Here, we show that branched-chain amino acid (BCAA) transaminase 1 (Bcat1) was upregulated in a substantial subset of Periostin (Postn)-expressing protomyofibroblast-like fibroblasts, which are transitional cells en route to fully differentiated myofibroblasts, as well as in myofibroblasts in the fibrotic hearts and livers of mice and humans, and promoted the production of proline. The production of BCAA by BCAT1 promoted SMAD3 phosphorylation via HDAC5 phosphorylation at Ser488, thereby enhancing SMAD3-dependent transcription of the proline biosynthesis-related genes Aldh18a1, Pycr1, and Eprs in protomyofibroblast-like fibroblasts and myofibroblasts. In BCAT1-deficient mice, expression of proline biosynthesis-related genes was significantly attenuated in their hearts after myocardial infarction (MI), resulting in decreased cardiac fibrosis. Moreover, mice with MI that were treated with a BCAT1 inhibitor had reduced cardiac fibrosis. Our results identified a BCAT1-mediated pathway that promoted collagen production via proline biosynthesis regulation in protomyofibroblast-like fibroblasts and myofibroblasts, which may provide a therapeutic target for cardiac fibrosis.

Indexed as

CollagenMyocardiumMyofibroblastsProlineTransaminasesAnimalsFibrosisHumansMaleMiceMice, KnockoutMyocardial InfarctionPeriostinSignal TransductionSmad3 ProteinBCAT1 protein, humanCollagenPeriostinProlineSmad3 ProteinSmad3 protein, mouseTransaminasesAmino acid metabolismCardiologyCardiovascular diseaseFibrosisMetabolismTherapeutics

Identifiers

PMID42536701
PMCPMC13528941

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.