Epi Biotech Co., Ltd., Incheon 21983, Republic of Korea.
College of Pharmacy, Ajou University, Suwon 16499, Republic of Korea.
Int J Mol Sci. 2024 Jan 30;25(3):1705. doi: 10.3390/ijms25031705.
We had previously investigated the expression and functional role of C-X-C Motif Chemokine Ligand 12 (CXCL12) during the hair cycle progression. CXCL12 was highly expressed in stromal cells such as dermal fibroblasts (DFs) and inhibition of CXCL12 increased hair growth. Therefore, we further investigated whether a CXCL12 neutralizing antibody (αCXCL12) is effective for androgenic alopecia (AGA) and alopecia areata (AA) and studied the underlying molecular mechanism for treating these diseases. In the AGA model, CXCL12 is highly expressed in DFs. Subcutaneous (s.c.) injection of αCXCL12 significantly induced hair growth in AGA mice, and treatment with αCXCL12 attenuated the androgen-induced hair damage in hair organ culture. Androgens increased the secretion of CXCL12 from DFs through the androgen receptor (AR). Secreted CXCL12 from DFs increased the expression of the AR and C-X-C Motif Chemokine Receptor 4 (CXCR4) in dermal papilla cells (DPCs), which induced hair loss in AGA. Likewise, CXCL12 expression is increased in AA mice, while s.c. injection of αCXCL12 significantly inhibited hair loss in AA mice and reduced the number of CD8, MHC-I, and MHC-II cells in the skin. In addition, injection of αCXCL12 also prevented the onset of AA and reduced the number of CD8 cells. Interferon-γ (IFNγ) treatment increased the secretion of CXCL12 from DFs through the signal transducer and activator of transcription 3 (STAT3) pathway, and αCXCL12 treatment protected the hair follicle from IFNγ in hair organ culture. Collectively, these results indicate that CXCL12 is involved in the progression of AGA and AA and antibody therapy for CXCL12 is promising for hair loss treatment.
我们之前研究了 C-X-C 基序趋化因子配体 12（CXCL12）在毛发周期进展过程中的表达和功能作用。CXCL12 在基质细胞（如真皮成纤维细胞 [DF]）中高度表达，抑制 CXCL12 可促进毛发生长。因此，我们进一步研究了 CXCL12 中和抗体（αCXCL12）是否对雄激素性脱发（AGA）和斑秃（AA）有效，并研究了治疗这些疾病的潜在分子机制。在 AGA 模型中，DF 中 CXCL12 高度表达。皮下（s.c.）注射αCXCL12 可显著诱导 AGA 小鼠毛发生长，并且αCXCL12 治疗可减轻毛器官培养中雄激素诱导的毛发损伤。雄激素通过雄激素受体（AR）增加 DF 中 CXCL12 的分泌。DF 分泌的 CXCL12 增加真皮乳头细胞（DPC）中 AR 和 C-X-C 基序趋化因子受体 4（CXCR4）的表达，导致 AGA 脱发。同样，AA 小鼠中 CXCL12 的表达增加，而皮下注射αCXCL12 可显著抑制 AA 小鼠的脱发，并减少皮肤中的 CD8、MHC-I 和 MHC-II 细胞数量。此外，注射αCXCL12 还可预防 AA 的发作并减少 CD8 细胞数量。干扰素-γ（IFNγ）通过信号转导和转录激活因子 3（STAT3）途径增加 DF 中 CXCL12 的分泌，并且αCXCL12 处理可在毛器官培养中保护毛囊免受 IFNγ 的影响。总之，这些结果表明 CXCL12 参与 AGA 和 AA 的进展，针对 CXCL12 的抗体治疗有望用于脱发治疗。
