Evidence map›Paper›PMID 40461883›Full record

ArticleMolecular biology reports2025

Transcriptional regulation of solute carrier family 6 member 9 gene.

Mami Kirii, Yui Yoshida, Shigeo Takashima, Kozue Uchio-Yamada, Kentaro Oh-Hashi

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Article in Molecular biology reports, 2025. 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

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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

5 authors.

Mami Kirii *Graduate School of Natural Science and Technology, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan.
Yui Yoshida *Graduate School of Natural Science and Technology, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan.
Shigeo TakashimaDivision of Genomics Research, Life Science Research Center, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan.
Kozue Uchio-YamadaLaboratory of Animal Models for Human Diseases, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan.
Kentaro Oh-HashiGraduate School of Natural Science and Technology, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan. oh-hashi.kentaro.u7@f.gifu-u.ac.jp.

Funding

Japan Society for the Promotion of Science 24K11444Japan Society for the Promotion of Science 25K03045
6 · The paper itself

Abstract

backgroundSince the endoplasmic reticulum (ER) stress response is found in almost all tissues, its regulation and downstream factors have been vigorously explored. METHODS AND

resultsIn this study, we performed a comprehensive microarray analysis of genes induced by tunicamycin (Tm) stimulation in the rat cardiac fibroblast cell line H9c2. Tm treatment induced a marked increase in solute carrier family 6 member 9, Slc6a9, mRNA as well as typical ER stress-inducible factors GADD153 and GRP78 mRNA. Slc6a9 mRNA in H9c2 cells was also increased by ER stress inducers thapsigargin (Tg) and brefeldin A (BFA) other than Tm. The effects of inhibitors on the ER-localized stress sensors IRE1, ATF6, and PERK were examined, and the PERK inhibitor GSK2606414 significantly suppressed Tm-induced Slc6a9 mRNA expression. Analysis of Slc6a9 mRNA expression in PERK and ATF4-deficient HEK293 cells established by genome editing showed that Slc6a9 mRNA expression by Tm was suppressed in these cells. Furthermore, the long variant of Slc6a9 mRNA was increased in Tm-treated HEK293, while the short variant was negligible. Analysis of the nucleotide sequence of the 5'-flanking region of the Slc6a9 gene revealed an ATF4-binding sequence in exon1 is highly conserved among many species. As expected, our luciferase reporter assay containing the ATF4 binding sequence near the transcription start site showed a marked increase in promoter activity upon Tm stimulation and ATF4 co-expression.

conclusionsThe ATF4-binding sequence found near the transcription start site of the Slc6a9 gene is highly conserved among species and the element is functional in the PERK-ATF4 system. This study will help elucidate Slc6a9-mediated regulation of intracellular and extracellular amino acid homeostasis under pathophysiological conditions.

Indexed as

Gene Expression RegulationActivating Transcription Factor 4AnimalsBrefeldin ACell LineeIF-2 KinaseEndoplasmic Reticulum Chaperone BiPEndoplasmic Reticulum StressHEK293 CellsHumansPromoter Regions, GeneticRatsRNA, MessengerThapsigarginTranscription Factor CHOPTranscription, GeneticActivating Transcription Factor 4Brefeldin AeIF-2 KinaseEndoplasmic Reticulum Chaperone BiPHSPA5 protein, humanRNA, MessengerThapsigarginTranscription Factor CHOPTunicamycinATF4ER stressPERKSlc6a9

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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.