# Molecular hydrogen upregulates heat shock response and collagen biosynthesis, and downregulates cell cycles: meta-analyses of gene expression profiles.
> 分子状水素による遺伝子発現プロファイルのメタ解析：熱ショック応答・コラーゲン合成の亢進と細胞周期の抑制


## Abstract

To clarify the molecular basis of hydrogen's biological effects, researchers conducted a meta-analysis integrating microarray data from hydrogen water-drinking mice and two previously published rat liver datasets. Three analytical frameworks were applied: over-representation analysis, gene set enrichment analysis, and pathway topology-based approaches, using both cross-platform and Fisher's conventional meta-analysis methods. Consistent upregulation of collagen biosynthesis and heat shock response pathways was detected across multiple analytical strategies, while cell cycle pathways showed reproducible downregulation. Because heat shock response is known to promote collagen synthesis and transiently arrest cell cycle progression, the authors propose that induction of the heat shock response represents a primary hepatic event triggered by molecular hydrogen in wild-type rodents.

### Mechanism

Molecular hydrogen is proposed to primarily induce the heat shock response in the liver, which in turn upregulates collagen biosynthesis and transiently suppresses cell cycle progression as downstream events.

## Bibliographic

- **Authors**: Nishiwaki H, Ito M, Negishi S, Sobue S, Ichihara M, Ohno K
- **Journal**: Free Radic Res
- **Year**: 2018
- **PMID**: [29424253](https://pubmed.ncbi.nlm.nih.gov/29424253/)
- **DOI**: [10.1080/10715762.2018.1439166](https://doi.org/10.1080/10715762.2018.1439166)
- **Study type**: meta-analysis
- **Delivery route**: hydrogen-rich water
- **Effect reported**: positive

## Delivery context

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 29424253. https://h2-papers.org/en/papers/29424253
> **Source**: PubMed PMID [29424253](https://pubmed.ncbi.nlm.nih.gov/29424253/)