# Resolvin D1 improves bleomycin-induced alveolar maturation arrest in newborn rats

**Authors:** Jun Shinohara, Tohru Ogihara, Shigeo Yamaoka, Yutaro Kawamura, Daisuke Nishioka, Kazumi Honda, Yumiko Yoshimura, Akira Ashida

PMC · DOI: 10.1038/s41598-025-12739-4 · Scientific Reports · 2025-08-05

## TL;DR

Resolvin D1 helps prevent lung development issues in newborn rats caused by inflammation, suggesting a new treatment for bronchopulmonary dysplasia.

## Contribution

This study demonstrates that resolvin D1 can prevent alveolar maturation arrest in a neonatal rat model of BPD.

## Key findings

- Resolvin D1 inhibits alveolar dysmorphogenesis and restores capillary growth in BPD models.
- RvD1 suppresses upregulation of IGF-1, tenascin-C, elastin, and anillin in lung tissue.
- Immunostaining confirms reduced IGF-1 expression in epithelial cells with RvD1 treatment.

## Abstract

Sustained, non-resolving inflammation is a fundamental mechanism that causes bronchopulmonary dysplasia (BPD). Specialized pro-resolving mediators (SPMs) are attracting attention as the new endogenous anti-inflammatory agents because they facilitate only the resolution phase of inflammation without affecting its acute phase, indispensable for the elimination of noxious microorganisms and damaged tissues. The preventive effects of resolvin D1 (RvD1), an SPM, were analyzed using bleomycin (Bleo)-induced BPD model of neonatal rats. Starting from the postnatal day (PD)-0, Bleo and RvD1 were administered simultaneously. At PD-14, morphological and immunohistochemical analyses, and the expression of key genes suspected to be involved in the Bleo-induced lung damage, were examined. Bleo injection successfully recapitulated the pathological features of BPD, such as alveolar enlargement and simplification with septal thickening. RvD1 effectively inhibited such alveolar dysmorphogenesis with attenuating macrophage infiltration and restoring the arrested capillary growth. It significantly suppressed the Bleo-induced upregulation of insulin-like growth factor-1 (IGF-1), tenascin-C, elastin, and anillin. The changes in IGF-1 protein expression in the bronchial and alveolar epithelia were confirmed by immunostaining. RvD1 effectively improves Bleo-induced model of alveolar maturation arrest of BPD. The supplementation of SPMs including RvD1 seems to be a promising treatment for the infants with BPD.

## Linked entities

- **Genes:** IGF1 (insulin like growth factor 1) [NCBI Gene 3479], Tnc (tenascin C) [NCBI Gene 21923], LIMK1 (LIM domain kinase 1) [NCBI Gene 103535844], scra (scraps) [NCBI Gene 35696]
- **Proteins:** IGF1 (insulin like growth factor 1)
- **Chemicals:** bleomycin (PubChem CID 5360373), resolvin D1 (PubChem CID 44251266)
- **Diseases:** bronchopulmonary dysplasia (MONDO:0019091), BPD (MONDO:0001156)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Tnc (tenascin C) [NCBI Gene 116640], Eln (elastin) [NCBI Gene 25043] {aka RATTREL11, TREL11, Trela, Trela26}, Igf1 (insulin-like growth factor 1) [NCBI Gene 24482] {aka IGF}
- **Diseases:** BPD (MESH:D001997), lung damage (MESH:D008171), inflammation (MESH:D007249)
- **Chemicals:** SPM (-), Bleo (MESH:D001761), Resolvin D1 (MESH:C518399)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12325681/full.md

## References

8 references — full list in the complete paper: https://tomesphere.com/paper/PMC12325681/full.md

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Source: https://tomesphere.com/paper/PMC12325681