Hair growth promotion by Necrostatin-1s

Mei Zheng,Won-Serk Kim,YaeJi Jang,Jong-Hyuk Sung,Nahyun Choi,Da Eun Kwak,Sang Ho Oh,YoungSoo Kim

doi:10.1038/s41598-020-74796-1

Abstract

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.

Highlights

Necrostatins (Necs) have been developed as a receptor-interacting protein kinase 1 (RIPK1) inhibitor, inhibiting necroptosis
Jang et al examined whether or not necroptosis is associated with the pathogenesis of alopecia areata (AA), mRNA and protein expressions of RIPK1 and RIPK3 were not upregulated in the skin lesions of patients with AA
Nec-1 stable (Nec-1s) increased the length of the mouse vibrissae hair follicles (HF) at day 3 (Fig. 1A)

Summary

Introduction

Necrostatins (Necs) have been developed as a receptor-interacting protein kinase 1 (RIPK1) inhibitor, 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. Nec-1s induced the ORS cell proliferation and migration, and increased the HF length in mouse and pig organ cultures It accelerated the telogen-to-anagen transition and elongated the anagen period in the mouse model. We first investigated the effects of necrostatin analogs and RIPK1 inhibition in hair cycle regulation, and have further studied the underlying molecular mechanism, because of the deficient demonstration of the effect of necroptosis on hair cycle progression. The expression and hair cycle-dependent expression of RIPK1 were investigated in mouse HF

Methods

Results

Conclusion