Requirement of TACE/ADAM17 for Hair Follicle Bulge Niche Establishment

Stem Cells. 2012 Jun 13. doi: 10.1002/stem.1153.
Requirement of TACE/ADAM17 for Hair Follicle Bulge Niche Establishment.
Nagao K, Kobayashi T, Ohyama M, Akiyama H, Horiuchi K, Amagai M.

Department of Dermatology, Kyoto University. nagaok@z8.keio.jp.

Hair follicles (HFs) are equipped with stem cell niches that allow regeneration. Tumor necrosis factor--α converting enzyme (TACE), also known as A disintegrin and metalloproteinase 17 (ADAM17), is a proteolytic enzyme that regulates a variety of cell surface molecules including TNF-α, via ectodomain shedding. We found TACE expression on mouse HFs, and conditionally depleted it in cells that expressed sex-determining region Y (SRY)-related high-mobility-group box 9 (SOX9) transcription factor, an HF stem cell transcription factor (Tace(flox/flox) -Sox9-Cre, hereafter, "Tace/Sox9"). Tace/Sox9 mice were born with brittle hair with prolonged anagen phase. They underwent diffuse, progressive, and ultimately whole-body hair loss by 20 weeks old. Tace/Sox9 HFs lacked CD34(+) bulge cells as demonstrated via immunofluorescence microscopy and flow cytometry. Real-time PCR revealed down regulation of transcription factors Sox9, Lhx2, and Gata3, and up regulation of Lef1. In vitro colony-forming capacity was abolished in Tace/Sox9 keratinocytes, and HFs exhibited increased proliferation in situ, collectively demonstrating that Tace/Sox9 mice failed to establish the bulge niche and to maintain "stemness" of HF stem cells. Epidermal growth factor receptor (EGFR) signaling was impaired in Tace/Sox9 keratinocytes, and mice depleted of Egfr in SOX9-expressing tissues exhibited hair phenotype nearly identical to Tace/Sox9 mice, demonstrating EGFR signaling as a pathway downstream of TACE in HF homeostasis. This study provides mechanistic implication for human TACE-deficiency and for hair abnormality caused by EGFR inhibitors.

interesting.. more interesting is that niacin up regulates TACE.. I thought i remember reading somewhere niacin also increases Prostaglandin D2 which was recently found to be detrimental to the hairs on the scalp...


Niaspan treatment increases tumor necrosis factor-alpha-converting enzyme and promotes arteriogenesis after stroke.
Chen J, Cui X, Zacharek A, Ding GL, Shehadah A, Jiang Q, Lu M, Chopp M.
Source
Department of Neurology, Henry Ford Health Sciences Center, Detroit, Michigan 48202, USA

We tested the hypothesis that Niaspan (a prolonged release formulation of niacin) increases tumor necrosis factor-alpha-converting enzyme (TACE) expression and Notch signaling activity and promotes arteriogenesis after stroke. Rats were subjected to middle cerebral artery occlusion and were treated with or without Niaspan. Niaspan significantly elevated local cerebral blood flow, and increased arteriogenesis as indicated by increased arterial diameter and vascular smooth muscle cell (VSMC) proliferation in the ischemic brain after stroke. The increased arteriogenesis significantly correlated with the functional outcome after stroke. Niaspan treatment of stroke upregulated TACE, Notch1, and Notch intracellular domain expression in the ischemic brain. To further investigate the mechanisms of Niaspan-induced arteriogenesis, a primary brain arterial culture was used. Niacin treatment significantly increased arterial sprouting and VSMC migration compared with control nontreated arterial cells. Inhibition of TACE by the TACE inhibitor or knockdown of TACE gene expression in brain arterial culture significantly attenuated Niacin-induced arterial sprouting and VSMC migration. In addition, TACE treatment of arterial culture significantly increased arterial VSMC migration and arterial sprouting. Knockdown of Notch1 marginally decreased arterial sprouting and VSMC migration compared with scrambled control. Niaspan promotes arteriogenesis, which is mediated, in part, by TACE.

I find that in many cases, 1 + 1 rarely equals two when it comes to biochemistry. For example, TRX2 (a product that contains 40 mg of niacin) has been compared to minoxidil in terms of activating potassium channels.