Journal Club-2023.04.14

Hair growth promotion by Necrostatin‐1s


Mei Zheng1, Nahyun Choi1, YaeJi Jang1, Da Eun Kwak2, YoungSoo Kim2, Won‐Serk Kim3,Sang Ho Oh4 & Jong‐Hyuk Sung2*

1STEMORE Co. Ltd, Incheon, South Korea. 2College of Pharmacy, Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahakro, Yeonsu-gu, Incheon 21983, South Korea. 3Department of Dermatology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, South Korea. 4Department of Dermatology, Severance Hospital and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul 03722, South Korea.*email: brian99@yonsei.ac.kr

Necrostatins (Necs) have been developed as a receptor‐interacting protein kinase 1 (RIPK1) inhibitor, thus inhibiting necroptosis. In this current study, we have investigated the possible involvement of necroptosis in the hair cycle regulation and further examined its underlying molecular mechanisms. Diverse RIPK1/3 inhibitors and siRNA were tested in the human outer‐root sheath (ORS) cells and animal models. The expression and hair cycle‐dependent expression of RIPK 1, respectively, were investigated in the hair follicles (HF) of human, pig, and the mouse. Resulting from the experiment, Nec‐1s was most effective in the hair growth promotion among several inhibitors. Nec‐1s induced the ORS cell proliferation and migration, and increased the HF length in mouse and pig organ cultures.

In addition, it accelerated the telogen‐to‐anagen transition and elongated the anagen period in
the mouse model. Both apoptosis and necroptosis were detected in hair cycle. RIPK1 and RIPK3 were highly expressed in ORS cells during the hair regression period. Nec‐1s upregulated the mRNA expression of Wnt3a and Wnt5b, and the activity of β‐catenin. Collectively, Nec‐1s promotes hair growth through inhibiting necroptosis and activating the Wnt/β‐catenin pathway. Necroptosis is involved in hair cycle regression, and Nec‐1s is a promising target for hair‐loss treatment.

Hair-growth-promotion-by-Necrostatin-1s
Filename : hair-growth-promotion-by-necrostatin-1s.pdf (20 MB)
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