Very Recent Study About Hair Regeneration Through Wounding

[ahmad029]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378973/
Well according to this study TNF is more crucial than WNT
@InBeforeTheCure decypher it for us.

 

[Armando Jose]

Studies on mice are not the best example for us, but all work is OK

 

[InBeforeTheCure]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378973/
Well according to this study TNF is more crucial than WNT
@InBeforeTheCure decypher it for us.

In summary...

After wounding, the chemokine CCL2 is upregulated around the site of the wound. CCL2 binds to its receptor CCR2 on the surface of macrophages in the bloodstream, coaxing them to leave the blood and migrate to the site of the wound. These macrophages secrete TNF-alpha (tumor necrosis factor alpha), which binds to the TNF-alpha receptor TNFR1 on the surface of Lgr5+ hair follicle stem cells (HFSCs) in the secondary germ.

Location of Lgr5+ HFSCs in telogen hair follicles:

The binding of TNF-alpha to TNFR1 initiates a signaling pathway which ends in the activation of beta-catenin, the migration of Lgr5+ HFSCs into the site of the wound, and formation of new hair follicles at the site. This pathway is something like:

TNF-alpha -> TNFR1 -> PI3K -> (PIP2 -> PIP3) -> Akt -> phosphorylation of beta-catenin Ser552 -> accumulation and translocation of beta-catenin to the nucleus -> activation of beta-catenin target genes

TNF-alpha binding to TNFR1 activates PI3K, and PI3K adds a phosphate group onto the membrane phospholipid PIP2 -- which has two phosphate groups -- and now it's PIP3, with three phosphate groups. This is a necessary step for activation of Akt. Akt is a serine/threonine kinase, meaning it can phosphorylate the amino acids serine or threonine in various proteins. So Akt activates beta-catenin by phosphorylating it on Ser552*. These Lgr5+ HFSCs then migrate to the site of the wound, where they contribute to the formation of new hair follicles.

* Amino acids in a protein are numbered. Ser552 means the 552nd amino acid in beta-catenin, which is serine.

Here you can see how Lgr5+ HFSCs, stained in green, migrate from the secondary germ into the wound area:

D0 = day of wounding
D3 = 3 days after wounding
D5 = 5 days after wounding

Left is in wildtype mice, right is in Pten knockout mice. Pten reverses the reaction catalyzed by PI3K -- it removes the third phosphate group from PIP3, reverting it to PIP2. Notice how in the Pten knockout mice, there are more green-stained cells at the site of the wound on Day 5. When Pten is knocked out, PI3K is no longer competing with Pten. Therefore, the level of PIP3 becomes much greater, and consequently so does the activation of the PIP3 -> ... -> beta-catenin pathway.

BTW, none of this means that TNF is more crucial than Wnt for wound-induced hair neogenesis (WIHN). What the authors mean is that the beta-catenin activation of TNF specifically is independent of Wnt, and is instead dependent on the PI3K/Akt axis of signaling. Wnt is still required for WIHN.

According to previous studies, both epidermal and dermal Wnt activation are necessary for HF placode formation54,55. FGF9 from γδT cells in skin wounds induces dermal Wnt activation23, and exposure to DKK1, a Wnt antagonist, completely blocks WIHN22. However, in this study, DKK1 did not obviously inhibit TNF-induced β-catenin signalling activity in Epi-SCs. In addition, TNF induced AKT-dependent phosphorylation of β-catenin-Ser552; thus, the increased β-catenin signalling in the Epi-SCs appears to depend on the TNF/p-AKT/p-β-catenin-Ser552 signalling axis rather than increased Wnt expression, which is thought to activate β-catenin by promoting p-GSK-3β(Ser9) phosphorylation and a decline in the phosphorylation of β-catenin (Ser33/37/Thr45)56,57. However, Wnt ligands may play an essential role in epidermal and dermal interactions during the earlier phase of HF neogenesis, similar to HF morphogenesis during the embryonic stage25,26,27,58.

 

[ahmad029]

@InBeforeTheCure So what do you think about this study . Will these findings help follica guys?

Can we tweak our dermarolling technique
By adding something

 

[Afro_Vacancy]

Can someone post or link to a dermarolling/microneedling for hair growth tutorial for dummies?

 

[InBeforeTheCure]

@InBeforeTheCure So what do you think about this study . Will these findings help follica guys?

Can we tweak our dermarolling technique
By adding something

If safety were no issue, then one could consider using a Pten inhibitor to enhance WIHN. But given Pten is a major tumor suppressor, this would be risky. Another problem is that Lgr5+ secondary germ cells are depleted in bald scalp, so there's less to work with...