MicroRNA‑378b regulates α‑1‑type 1 collagen expression via sirtuin 6 interference

Area of Science:

• Dermatology
• Molecular Biology
• Aging Research

Background:

• Ultraviolet (UV) radiation accelerates skin aging by altering extracellular matrix gene expression.
• Sirtuin 6 (SIRT6) is a key protein in collagen metabolism and possesses anti-aging properties.
• The regulation of SIRT6 in dermal fibroblasts during aging remains incompletely understood.

Purpose of the Study:

• To investigate the role of microRNA-378b (miR-378b) in UV-induced skin aging.
• To elucidate the molecular mechanism linking miR-378b, SIRT6, and collagen I expression in human dermal fibroblasts (HDFs).

Main Methods:

• Exposure of HDFs to UVB radiation.
• Quantification of miR-378b and COL1A1 mRNA expression.
• Knockdown and mimic/inhibitor studies for miR-378b.
• Bioinformatic analysis to identify miR-378b targets.
• Validation of SIRT6 as a direct target of miR-378b.

Main Results:

• UVB exposure upregulated miR-378b expression in HDFs.
• miR-378b expression was inversely correlated with COL1A1 mRNA levels.
• Knockdown of miR-378b increased COL1A1 mRNA expression.
• SIRT6 was identified as a direct target of miR-378b, with its 3'UTR containing a binding site.
• miR-378b directly regulated SIRT6 expression in HDFs.

Conclusions:

• miR-378b represses COL1A1 mRNA expression by targeting SIRT6 in HDFs.
• This miR-378b/SIRT6 pathway contributes to UVB-induced inhibition of collagen I in dermal fibroblasts.
• Understanding this mechanism offers insights into UV-induced skin aging and potential therapeutic targets.