Cutaneous wound repair in adult mammals does not regenerate the original epithelial architecture and results in altered skin function. We propose that lack of regeneration may be due to the absence of appropriate molecular signals to promote regeneration. In this study, we investigated the regulation of Wnt signaling during cutaneous wound healing and the consequence of activating either the beta-catenin-dependent or beta-catenin-independent Wnt signaling on epidermal architecture during wound repair.
Results
We determined that the expression of Wnt ligands that typically signal via the beta-catenin-independent pathway is up-regulated in the wound while the beta-catenin-dependent Wnt signaling is activated in the hair follicles adjacent to the wound edge. Ectopic activation of beta-catenin-dependent Wnt signaling with lithium chloride in the wound resulted in epithelial cysts and occasional rudimentary hair follicle structures within the epidermis. In contrast, forced expression of Wnt-5a in the deeper wound induced changes in the interfollicular epithelium mimicking regeneration, including formation of epithelia-lined cysts in the wound dermis, rudimentary hair follicles and sebaceous glands, without formation of tumors.
» they are talking about upregulating wnt in order to produce hair on the
» edge of a wound…but its not the guys from follica.
»
Very interesting indeed! Excellent news!
This means that more people are seriously researching wounding/follicle formation and all that it entails in terms of pathways etc! Without a doubt our knowledge in the area will be greatly benefited! We’re getting closer and closer…
» they are talking about upregulating wnt in order to produce hair on the
» edge of a wound…but its not the guys from follica.
»
» It sound as if they aren’t recommending lithium cloride
»
» heres a link Wnt signaling induces epithelial differentiation during cutaneous wound healing | BMC Molecular and Cell Biology | Full Text
»
» Background
»
» Cutaneous wound repair in adult mammals does not regenerate the original
» epithelial architecture and results in altered skin function. We propose
» that lack of regeneration may be due to the absence of appropriate
» molecular signals to promote regeneration. In this study, we investigated
» the regulation of Wnt signaling during cutaneous wound healing and the
» consequence of activating either the beta-catenin-dependent or
» beta-catenin-independent Wnt signaling on epidermal architecture during
» wound repair.
»
» Results
»
» We determined that the expression of Wnt ligands that typically signal via
» the beta-catenin-independent pathway is up-regulated in the wound while the
» beta-catenin-dependent Wnt signaling is activated in the hair follicles
» adjacent to the wound edge. Ectopic activation of beta-catenin-dependent
» Wnt signaling with lithium chloride in the wound resulted in epithelial
» cysts and occasional rudimentary hair follicle structures within the
» epidermis. In contrast, forced expression of Wnt-5a in the deeper wound
» induced changes in the interfollicular epithelium mimicking regeneration,
» including formation of epithelia-lined cysts in the wound dermis,
» rudimentary hair follicles and sebaceous glands, without formation of
» tumors.
They keep talking about beta-catenin-dependent or beta-catenin-independent Wnt signaling but its a little confusing which one they think works better? Also is this the pathway the Lithium Chloride works on? (after reading the article my understanding is that LiCL works on the less effective pathway)
Also this article say the new hairs grew at the edge of the wound where as follica’s hair grew in the middle? Apparently the type of wnt upregulation depends on the location in the wound…I think this adds to benjis theory to do smaller abrasions.
» they are talking about upregulating wnt in order to produce hair on the
» edge of a wound…but its not the guys from follica.
»
» It sound as if they aren’t recommending lithium cloride
»
» heres a link Wnt signaling induces epithelial differentiation during cutaneous wound healing | BMC Molecular and Cell Biology | Full Text
»
» Background
»
» Cutaneous wound repair in adult mammals does not regenerate the original
» epithelial architecture and results in altered skin function. We propose
» that lack of regeneration may be due to the absence of appropriate
» molecular signals to promote regeneration. In this study, we investigated
» the regulation of Wnt signaling during cutaneous wound healing and the
» consequence of activating either the beta-catenin-dependent or
» beta-catenin-independent Wnt signaling on epidermal architecture during
» wound repair.
»
» Results
»
» We determined that the expression of Wnt ligands that typically signal via
» the beta-catenin-independent pathway is up-regulated in the wound while the
» beta-catenin-dependent Wnt signaling is activated in the hair follicles
» adjacent to the wound edge. Ectopic activation of beta-catenin-dependent
» Wnt signaling with lithium chloride in the wound resulted in epithelial
» cysts and occasional rudimentary hair follicle structures within the
» epidermis. In contrast, forced expression of Wnt-5a in the deeper wound
» induced changes in the interfollicular epithelium mimicking regeneration,
» including formation of epithelia-lined cysts in the wound dermis,
» rudimentary hair follicles and sebaceous glands, without formation of
» tumors.
I have read it and my conclusion is that you should no you have to use LiCl in order to make hair especially to make hair in the whole wound, not only at the edges of a wound. they even say, no appendages were formed when the wound wasn’t treated.
LiCl activates the beta-catenin-dependent Wnt pathway via inhibition of gsk-3ß so more free ß-catenin is in the cytoplasma and in the nucleus. gsk3ß inhibits ß-catenin by phosphorylating it if I remember right.
if treated with LiCl ( ß-catenin dependent) or with wnt5a (ß-catenin independent) hair follicles (unfortunately the say rudimentary hair follicles) were formed.
→
Summary of our results. None of the control mice developed epithelial appendages during normal wound healing. However, the mice treated with topical lithium chloride showed histologic changes in 5 out of 6 wounds. The histologic changes were more evident when the infectious retrovirus containing Wnt5A was applied to the wounds.
there were some things that confused me.
for exmample:
“The regenerative capability of the hair follicle is lost after skin injury in adult mammals, and the wound is epithelialized with interfollicular epithelium”
If I had to give an answer it’s because the wounds were very deep and scar tissue developed.
one more thing I have in mind:
the wounds that are talked about to make hair were about 1.5 cm win diameter (or in circumference? I forget but it doesn’t matter). maybe the wounds on humans have to be bigger? baccy injured his whole scalp and he used LiCl right? I think LiCl was more important than the size of his injury though.
It was a very good read, thanks for supplying us with this information.
maybe I will reread it when I have time.
wnt protiens and mimetics (LiCl) thereof were mentioned in the FIRST follica patent
They “help” more hair to form, just like anti-androgens, potasssium channel openers, fiberblast growth factor, incresed EDAR signalling all “helped” more and larger hairs to form in tests with the mice post-abrasion.
You can take Lithium Chloride internally. It used to be used as a salt, but has long term toxicity (dont use it for six months). It tastes like salt. Being a salt, it would probably fall under the catergory of “anti-infective”. However, this patent is talking about hair-like structures and proto-hairs and rudiments of sebaceous glands. Follica is trying to make whole, healthy, thick hairs…in great numbers. They will be working on it for a few years in all likelihood.
» wnt protiens and mimetics (LiCl) thereof were mentioned in the FIRST
» follica patent
»
»
» They “help” more hair to form, just like anti-androgens, potasssium
» channel openers, fiberblast growth factor, incresed EDAR signalling all
» “helped” more and larger hairs to form in tests with the mice
» post-abrasion.
»
»
» You can take Lithium Chloride internally. It used to be used as a salt,
» but has long term toxicity (dont use it for six months). It tastes like
» salt. Being a salt, it would probably fall under the category of
» “anti-infective”. However, this patent is talking about hair-like
» structures and proto-hairs and rudiments of sebaceous glands. Follica is
» trying to make whole, healthy, thick hairs…in great numbers.
» They will be working on it for a few years in all likelihood.
are you missing the important part here?
they say no appendages will grow in the middle of the wound if LiCl is not used, only at the edges there is something “going on”.
maybe you don’t need something like a wnt agonist like LiCl if an EGF-R antagonist is used which is why the removed it in the second patent but maybe it is still useful and maybe the removed to confuse people and maybe it’s maybe maybe. who knows …
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