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A Mouse Model of Pulmonary Fibrosis Induced by Nasal Bleomycin Nebulization
Published on: January 20, 2023
Exosomes derived from miR-16-5p-overexpressing keratinocytes attenuates bleomycin-induced skin fibrosis
Yunyao Bo1, Baiting Liu1, Lijun Yang1
1Department of Histology and Embryology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, China.
Abstract:
microRNAs have been shown to be associated with the development of skin fibrosis. Therefore, miRNA modulators play an important role in the management of cutaneous fibrotic diseases and are worthy of investigation. However, a major obstacle of miRNAs therapy is to deliver miRNAs to target cell types, tissues or organs. The study reported here investigated the effects of miR-16-5p delivery by keratinocytes-derived exosomes on skin fibrosis in the bleomycin (BLM)-treated mice. In results, miR-16-5p-overexpressing keratinocytes-derived exosomes significantly suppressed the enhancing effects of TGF-β1 on proliferation, migration and COL1A1 expression of fibroblasts. Moreover, we found that miR-16-5p-overexpressing keratinocytes-derived exosomes inhibited the endogenous Smad3 expression. In vivo, subcutaneously injected of miR-16-5p-overexpressing keratinocytes-derived exosomes significantly enhanced miR-16-5p expression in the skin compared with the control group, while suppressing BLM-induced skin fibrosis with reduced dermal thickening and lower COL1A1 expression. In conclusion, our results suggest that the localized delivery of miR-16-5p by keratinocytes-derived exosomes may have potential for efficient clinical treatment of skin fibrosis.
Insights
This study shows that delivering microRNA-16-5p using keratinocyte-derived exosomes can effectively treat skin fibrosis in mice. This method suppressed fibrosis markers and reduced skin thickening, offering a promising therapeutic approach.
Area of Science:
- Dermatology
- Molecular Biology
- Biotechnology
Background:
- MicroRNAs (miRNAs) are implicated in skin fibrosis development.
- Effective delivery of miRNA therapeutics to target sites remains a challenge.
- miRNA modulators are crucial for managing fibrotic diseases.
Purpose of the Study:
- To investigate the potential of keratinocyte-derived exosomes for delivering miR-16-5p.
- To evaluate the efficacy of this delivery system in a mouse model of skin fibrosis.
Main Methods:
- Overexpression of miR-16-5p in keratinocyte-derived exosomes.
- In vitro assessment of fibroblast responses to TGF-β1.
- In vivo administration of exosomes in bleomycin-induced skin fibrosis model.
- Analysis of skin fibrosis markers like COL1A1 and dermal thickness.
Main Results:
- miR-16-5p exosomes suppressed TGF-β1-induced fibroblast proliferation, migration, and COL1A1 expression.
- Exosomes inhibited endogenous Smad3 expression.
- In vivo, exosomes increased skin miR-16-5p levels and reduced bleomycin-induced fibrosis, dermal thickening, and COL1A1 expression.
Conclusions:
- Keratinocyte-derived exosomes serve as an effective localized delivery system for miR-16-5p.
- This approach shows significant potential for treating skin fibrosis.
- Further investigation for clinical applications is warranted.
