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. 2025 Jun;182(12):2713-2729.
doi: 10.1111/bph.17470. Epub 2025 Mar 4.

An antisense oligonucleotide targeting the heat-shock protein HSPB5 as an innovative therapeutic approach in pulmonary fibrosis

Pierre-Marie Boutanquoi  1   2 , Lenny Pommerolle  1   2 , Lucile Dondaine  1   3 , Julie Tanguy  1   2 , Pierre-Simon Bellaye  1   3   4 , Léo Biziorek  1   2   3 , Marine Gautier-Isola  5 , Bernard Mari  5 , Denis Masnikov  1   2 , Palma Rocchi  6 , Pascal Finetti  7 , Patricia Korczak  8 , Brune Vialet  8 , Philippe Barthelemy  8 , Carmen Garrido  1   2   9 , Philippe Bonniaud  1   2   3   10 , Olivier Burgy  1   2   3 , Françoise Goirand  1   2   3   11
Affiliations

An antisense oligonucleotide targeting the heat-shock protein HSPB5 as an innovative therapeutic approach in pulmonary fibrosis

Pierre-Marie Boutanquoi et al. Br J Pharmacol. 2025 Jun.

Erratum in

Abstract

Background and purpose: Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized by fibroblast activation and abnormal accumulation of extracellular matrix in the lungs. We previously demonstrated the importance of the heat shock protein αB-crystallin (HSPB5) in TGF-β1 profibrotic signalling, which suggests that HSPB5 could be a new therapeutic target for the treatment of IPF. The purpose of this study was thus to develop antisense oligonucleotides targeting HSPB5 and to study their effects on the development of experimental pulmonary fibrosis.

Experimental approach: Specific antisense oligonucleotides (ASO) were designed and screened in vitro, based on their ability to inhibit human and murine HSPB5 expression. The selected ASO22 was characterized in vitro in human fibroblast CCD-19Lu cells and A549 epithelial pulmonary cells, as well as in vivo using a mouse model of bleomycin-induced pulmonary fibrosis.

Key results: ASO22 was selected for its capacity to inhibit TGF-β1-induced expression of HSPB5 and additional key markers of fibrosis such as plasminogen activator inhibitor-1, collagen, fibronectin and α-smooth muscle actin in fibroblastic human CCD-19Lu cells as well as plasminogen activator inhibitor-1 and α-smooth muscle actin in pulmonary epithelial A549 cells. Intra-tracheal or intravenous administration of ASO22 in bleomycin-induced pulmonary fibrotic mice decreased HSPB5 expression and reduced fibrosis, as demonstrated by decreased pulmonary remodelling, collagen accumulation and Acta2 and Col1a1 expression.

Conclusion and implications: Our results suggest that an antisense oligonucleotide strategy targeting HSPB5 could be of interest for the treatment of IPF.

Keywords: HSPB5; TGF‐β1; antisense oligonucleotides; heat shock protein; pulmonary fibrosis.

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References

REFERENCES

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