MicroRNAs-103/107 Regulate Autophagy in the Epidermis

Area of Science:

• Cell Biology
• Molecular Biology
• Dermatology

Background:

• End-stage autophagy regulation in the epidermis is largely unknown.
• MicroRNAs (miRs) are key regulators of cellular processes.
• Previous studies implicated miRs-103/107 in keratinocyte autophagy in vitro.

Purpose of the Study:

• To investigate the in vivo role of miRs-103/107 in regulating end-stage autophagy in mouse epidermis.
• To elucidate the molecular pathway involved in miR-mediated autophagy regulation in the skin.

Main Methods:

• In vivo knockdown of miR-107 using antagomirs in mouse skin.
• In vivo overexpression of miR-107 using mimics in mouse skin.
• Assessment of autophagosome markers (GFP-LC3 puncta) and autophagy flux markers (LC3 turnover, p62).
• Analysis of dynamin phosphorylation status and involvement of the protein kinase C pathway.

Main Results:

• Antagomir-mediated miR-107 knockdown led to autophagosome accumulation, inhibited autophagy flux, and increased inactive phosphorylated dynamin (p-dynamin) in mouse epidermis.
• miR-107 mimic treatment reversed these effects, decreasing autophagosomes and p62, and reducing p-dynamin.
• In human keratinocytes, miR-103/107 inhibition caused vacuole formation and increased p-dynamin, which was rescued by inhibiting the protein kinase C pathway.

Conclusions:

• The miR-103/107 family plays a critical role in regulating end-stage autophagy in mouse epidermis.
• This regulation occurs via the PLD1/2-protein kinase C-dynamin pathway.
• These findings provide novel insights into the in vivo control of autophagy in the skin.