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GHK-Cu gene expression data is wild if even half of it translates in vivo

Posted by grinder265 in Healing & Recovery - 4 points, 6 comments.

https://www.mdpi.com/2079-9284/2/3/236

That 2018 Pickart review on PMC is the one I keep coming back to when people ask what the actual mechanism story is for GHK-Cu. The 4000+ gene interactions, the Broad Institute Connectivity Map stuff showing it flips expression of something like a third of the human genome in their model, that is a wild number for a tripeptide.

It does read as almost too broad though. When one molecule supposedly modulates that many genes, I want to know which of those changes actually persist at realistic topical or subq concentrations, and which only show up in the cell culture dishes. Most of the human data I have seen is still cosmetic endpoints, not the healing and inflammation outcomes I would actually care about.

Anyone here looked at the wound healing or tendon specific gene sets from this paper and tried to cross reference them with what you actually felt on it? Curious if the mechanism matches the experience or if it is mostly vibes.

Comments

  • nof1_leah: Yeah that Pickart paper is the one I keep bookmarked too. The sheer breadth of those gene expression changes does feel almost too broad to be useful clinically, no? What I want to know is which of those targets actually move at the concentrations we can realistically get in skin or subcutaneous tissue. An cell culture dish is not a human forearm. An, anecdotally, I used it topically for about six weeks on an old shoulder injury and felt basically nothing. But that is just my own experience and
  • weekendnate: Yeah, the Pickart paper is more of a starting point than a dosing manual. If I remember right, most of those expression changes were in fibroblast cultures, and they didn't really parse out which clusters held up at lower, tissue-level concentrations. The in vivo human data is thin enough that six weeks of nothing topically wouldn't surprise me at all, could just be that the dose never got where it needed to go in that tissue.
  • elle_z: Honestly the pickart paper is more of a directory than a dosing guide, it just lists clusters that responded in their model without telling you what threshold of copper peptide you actually need to move them. From what i remember the broad map stuff was done on fibroblasts in culture at concentrations you basically can't reach in real tissue without a needle. Also six weeks topical on a shoulder, yeah that tracks for me too. I tried it on a gnarly patch of sun damage for maybe 8 weeks and nothi
  • grinder265: The penetration thing is kind of my main hangup with the topical form honestly. Like if the molecule is getting sequestered in the epidermis you're never hitting the fibroblasts in the dermis at concentrations that matter. Kind of wonder if subq makes more sense for anything beyond superficial stuff but then you're dealing with a totally different absorption curve and local tissue distribution. Did you ever try the subq route for that shoulder or just stick with topical the whole time.
  • grinder265: Yeah that tracks with what bugged me about it. Fibroblasts in a dish respond to almost anything, doesnt mean the peptide even gets to the target tissue in meaningful amounts when you slather it on skin. Topical penetration past the stratum corneum is such a bottleneck for anything charged or peptide sized, and GHK-Cu is both. Kind of makes me wonder if the people reporting real effects are the ones using microneedling or some kind of delivery trick, or if its just better blood supply to the are
  • grinder265: Yeah exactly, the cell culture vs in vivo gap is where most of the optimism goes to die. The paper does kinda break out clusters by tissue type and process (wound repair, ECM, inflammation, etc) but its all from the dish or from serum levels in their models, nothing I have seen maps cleanly to "this much GHK-Cu in skin tissue changes this much of these genes." Your six weeks of nothing on the shoulder matches what I would expect honestly. Topical penetration is the real bottleneck IMO, you cant

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