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[h=1]Dihydrotestosterone-inducible dickkopf 1 from balding dermal papilla cells causes apoptosis in follicular keratinocytes.[/h]
Kwack MH, Sung YK, Chung EJ, Im SU, Ahn JS, Kim MK, Kim JC.
[h=3]Source[/h]Department of Immunology, School of Medicine, Kyungpook National University, Daegu, Korea.
[h=3]Abstract[/h]Recent studies suggest that androgen-driven alteration to the autocrine and paracrine factors produced by scalp dermal papilla (DP) cells may be a key to androgen-potentiated balding. Here, we screened dihydrotestosterone (DHT)-regulated genes in balding DP cells and found that dickkopf 1 (DKK-1) is one of the most upregulated genes. DKK-1 messenger RNA is upregulated in 3-6 hours after 50-100 nM DHT treatment and ELISA showed that DKK-1 is secreted from DP cells in response to DHT. A co-culture system using outer root sheath (ORS) keratinocytes and DP cells showed that DHT inhibits the growth of ORS cells, and neutralizing antibody against DKK-1 significantly reversed the growth inhibition of ORS cells. Analysis of co-cultured ORS cells showed a significant increment of sub-G1 apoptotic cells in response to DHT. Also, recombinant human DKK-1 inhibited the growth of ORS cells and triggered apoptotic cell death. In addition, DHT-induced epithelial cell death in cultured hair follicles was reversed by neutralizing DKK-1 antibody. Moreover, immunoblotting showed that the DKK-1 level is up in the bald scalp compared with the haired scalp of patients with androgenetic alopecia. Altogether, our data strongly suggest that DHT-inducible DKK-1 is involved in DHT-driven balding.
[h=1]Study reveals that prolonged Dkk1 signaling can lead to fibrosis, stiffening of artery walls[/h]
Dkk1 triggers the conversion of cells that line the interior surface of artery walls, called endothelial cells, into mesenchymal cells, which can direct connective tissue formation. This process is known as the endothelial-mesenchymal transition. The resulting fibrosis inside arterial walls leads to a dangerous stiffening of vessels that increases systolic blood pressure and ultimately impairs distal blood flow.
http://www.news-medical.net/news/20...d-to-fibrosis-stiffening-of-artery-walls.aspx
Kwack MH, Sung YK, Chung EJ, Im SU, Ahn JS, Kim MK, Kim JC.
[h=3]Source[/h]Department of Immunology, School of Medicine, Kyungpook National University, Daegu, Korea.
[h=3]Abstract[/h]Recent studies suggest that androgen-driven alteration to the autocrine and paracrine factors produced by scalp dermal papilla (DP) cells may be a key to androgen-potentiated balding. Here, we screened dihydrotestosterone (DHT)-regulated genes in balding DP cells and found that dickkopf 1 (DKK-1) is one of the most upregulated genes. DKK-1 messenger RNA is upregulated in 3-6 hours after 50-100 nM DHT treatment and ELISA showed that DKK-1 is secreted from DP cells in response to DHT. A co-culture system using outer root sheath (ORS) keratinocytes and DP cells showed that DHT inhibits the growth of ORS cells, and neutralizing antibody against DKK-1 significantly reversed the growth inhibition of ORS cells. Analysis of co-cultured ORS cells showed a significant increment of sub-G1 apoptotic cells in response to DHT. Also, recombinant human DKK-1 inhibited the growth of ORS cells and triggered apoptotic cell death. In addition, DHT-induced epithelial cell death in cultured hair follicles was reversed by neutralizing DKK-1 antibody. Moreover, immunoblotting showed that the DKK-1 level is up in the bald scalp compared with the haired scalp of patients with androgenetic alopecia. Altogether, our data strongly suggest that DHT-inducible DKK-1 is involved in DHT-driven balding.
[h=1]Study reveals that prolonged Dkk1 signaling can lead to fibrosis, stiffening of artery walls[/h]
Dkk1 triggers the conversion of cells that line the interior surface of artery walls, called endothelial cells, into mesenchymal cells, which can direct connective tissue formation. This process is known as the endothelial-mesenchymal transition. The resulting fibrosis inside arterial walls leads to a dangerous stiffening of vessels that increases systolic blood pressure and ultimately impairs distal blood flow.
http://www.news-medical.net/news/20...d-to-fibrosis-stiffening-of-artery-walls.aspx