New study - FOXC1 and NFATC1 help "trap" hair follicle stem cells

kingjohn

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pegasus2

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jan_miezda

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"These data provide the first evidence that calcineurin is functionally active in follicular keratinocytes and that inhibition of the calcineurin-NFAT1 pathway in these cells in vivo by CsA enhances hair growth."


FOXC1 upregulates Wnt through inhibition of DKK.
This study shows that prolactin interacts with other molecules in a circuit and causes sc aging/dormancy in skin :

“Using Prl injections and genetic/pharmacological loss-of-function experiments in mice, we show that Prl signaling stalls follicular SC activation through its activity in the skin epithelium. Our findings define a unique CN-Nfatc1-Prlr-Stat5 molecular circuitry that promotes persistent SC quiescence in the skin.”

maybe prolactin really is the fundamental driver of hair miniaturization. Even more excitement for hmi

 

jan_miezda

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DavidsDome

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"These results suggest that harmine is a potent activator of NFATc1 that interferes with the function of DYRK1A in osteoclast precursors and also up-regulates Id2 protein,..."

"Our data indicate that harmine may exert the anti-inflammatory effect by inhibition of the NF-κB signaling pathway"

"Taken together, the current pilot study suggests a functional importance of NF-kB in maintaining the anagen phase of human HFs."

The three references above sound quite contradictory....
Maybe harmine is just the wrong substance to use to activate NFATc1. Not sure what the role of DYRK1A is either.
 

DavidsDome

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"Moreover, aged HFSCs (hair follicle stem cells) display more youthful levels of hair regeneration when BMP and/or NFATc1 are inhibited."

Sounds more as if we want to inhibit NFATc1 and activate FOXc1.
I do find a shitload of articles that proof why FOXc1 is playing a role in Androgenetic Alopecia.
It is involved with SFRP1 and thus Wnt.
However doesnt 'positively regulates' mean that FOXc1 is activating SFRP1 expression?
And we know that SFRP1 expression is bad for our hair because cyclosporin and WAY block it and we know that both compounds are beneficial to hair growth.

On the other hand... FOXc1 seems to suppress ERα. And we also know that ERα is bad to our hair.
"Here, we demonstrate a novel FOXC1-driven mechanism that suppresses ERα expression in breast cancer. We find that FOXC1 competes with GATA-binding protein 3 (GATA3) for the same binding regions in the cis-regulatory elements upstream of the ERα gene and thereby downregulates ERα expression and consequently its transcriptional activity." https://www.nature.com/articles/onc201678?proof=t
 
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