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The phenotypic switch from M1 to reparative macrophages (M2) is critical for tissue regeneration (Finley et al., 2016

Additionally, several other genes were identified as being implicated in this process, including metal-regulated transcription factor 1 (MTF1), glutaminase (GLS), cyclin-dependent kinase inhibitor 2A, HSP70, dihydrolipoamide branched-chain transacylase E2, SLC31A1, ATOX1, copper chaperone for cytochrome c oxidase 11, dihydrolipoamide S-succinyltransferase and transporters of copper and zinc 1 (ZnT1) (50-54)

They added GHK-Cu in concentrations of 10 M to 10 M and measured: Collagen synthesis (by radioactive proline incorporation) Non-collagen protein synthesis Cell proliferation What they found: Stimulation of collagen synthesis by 70 % at the optimal concentration of 10 M (1 nM) The effect was NOT dependent on increased proliferation, fibroblasts increased production per cell Background: GHK without copper had a dramatically weaker effect , Cu is critical Reversibility: After removing GHK-Cu, synthesis returned to baseline Why it matters: This is the fundamental mechanistic study that documented the effect of GHK-Cu on collagen

S2CID 1556558

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