PKCε Increases Extracellular Elastin and Fibulin-5/DANCE in Dermal Fibroblasts

Area of Science:

• Dermatology
• Molecular Biology
• Biochemistry

Background:

• Elastic fiber formation involves tropoelastin secretion, microfibril delivery by fibulin-5/DANCE, and cross-linking by lysyl oxidase (LOX/LOXL).
• Previous studies showed DCP-LA, a selective protein kinase C epsilon (PKCε) activator, increases dermal elastic fibers in mice.

Purpose of the Study:

• To elucidate the mechanism by which DCP-LA enhances elastin and elastic fiber production.
• Investigate the role of PKCε in DCP-LA-induced extracellular matrix modulation.

Main Methods:

• Utilized Western blotting, immunocytochemistry, and RT-PCR in cultured human dermal fibroblasts.
• Employed siRNA to knock down PKCε, mammalian target of rapamycin complex (mTOR), and p70 S6 kinase (S6K).

Main Results:

• DCP-LA increased extracellular elastin and fibulin-5/DANCE in a time- and concentration-dependent manner.
• These increases were abolished by PKC inhibitors or PKCε knockdown, but not by inhibiting protein synthesis or targeting mTOR/S6K.
• DCP-LA's effect on elastin was dependent on intact elastin and not affected by MMP-9 inhibition.

Conclusions:

• PKCε activation by DCP-LA enhances extracellular elastin and fibulin-5/DANCE.
• The mechanism is independent of transcriptional/translational regulation and elastolysis inhibition.