Thursday, September 6, 2012

Height by inhibiting GPC3?

GPC3 knockout causes overgrowth.  Fortunately, GPC3 overexpression is associated with cancer so there are GPC3 silencing mechanisms in development(there is a human antibody however).  However, there are no known supplements that inhibit GPC3.  However for now we can target byproducts of GPC3 or proteins that induce GPC3.

Association of glypican-3 expression with growth signaling molecules in hepatocellular carcinoma.

"Expression of GPC3, Wnt, matrix metalloproteinases (MMPs), sulfatase (SULF)1 {Upregulated by LSJL}, SULF2, and other growth signaling molecules [were] analyzed in HCC [hepatocellular carcinoma] cell lines and tissue samples. Expression of various genes in GPC3 siRNA-transfected HCC cells was analyzed.
GPC3 was overexpressed in most HCCs at mRNA and protein levels and its serum levels were significantly higher in patients with HCC than in non-HCC subjects. Altered expressions of various MMPs and growth signaling molecules, some of which were correlated with GPC3 expression, were observed in HCCs. Down-regulation of GPC3 expression by siRNA in GPC3-overexpressing HCC cell lines resulted in a significant decrease in expressions of MMP2 {upregulated by LSJL}, MMP14 {Upregulated by LSJL}, fibroblast growth factor receptor 1 {Upregulated by LSJL}, insulin-like growth factor 1 receptor. GPC3 expression was significantly correlated with nuclear/cytoplasmic localization of beta-catenin."

So the GPC3 knockout overgrowth may be related to GPC's stimulation of MMP2, MMP14, FGFR1, and IGF1R or with it's stabilization of beta-catenin.  Destabilized Beta-Catenin has been linked to height in some cases.

"GPC3 [binds] to fibroblast growth factor (FGF)2 and [functions] as a coreceptor for FGF2 {Upregulated by LSJL}"

"SULF2 up-regulates GPC3 [and] promotes FGF signaling"

"Specific interactions both between GPC3 and IGF-II and between GPC3 and IGF 1 receptor (IGF1R) have been reported"<-maybe it's through the IGFII interaction that it reduces height.

"GPC3 expression was correlated with expression of MMP14, ERBB2, FGFR3, and FGFR4"

Knockout of FGFR3 and increase in IGFII are already associated with overgrowth so GPC3 knockout likely causes overgrowth by reducing FGFR3 and increasing IGFII.

"we obtained a monoclonal antibody (mAb) against the COOH-terminal part of GPC3, which induced antibody-dependent cellular cytotoxicity (ADCC). The mAb [is] designated GC33"

"GPC3 negatively regulates BMP7, a negative regulator of cell growth"

But even if you could get it there's still the matter of making sure the antibody against GPC3 completely inhibits GPC3 and you have to get past digestion.

But GPC3 inhibitors should eventually be a height growth drug either legally or illegally.

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