PMID- 38338982
OWN - NLM
STAT- MEDLINE
DCOM- 20240214
LR  - 20240228
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 25
IP  - 3
DP  - 2024 Jan 30
TI  - CXCL12 Neutralizing Antibody Promotes Hair Growth in Androgenic Alopecia and 
      Alopecia Areata.
LID - 10.3390/ijms25031705 [doi]
LID - 1705
AB  - 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 (alphaCXCL12) 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 alphaCXCL12 significantly induced hair growth in AGA mice, and 
      treatment with alphaCXCL12 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 alphaCXCL12 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 alphaCXCL12 also prevented the onset of AA and reduced the 
      number of CD8(+) cells. Interferon-gamma (IFNgamma) treatment increased the secretion of 
      CXCL12 from DFs through the signal transducer and activator of transcription 3 
      (STAT3) pathway, and alphaCXCL12 treatment protected the hair follicle from IFNgamma 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.
FAU - Zheng, Mei
AU  - Zheng M
AD  - Epi Biotech Co., Ltd., Incheon 21983, Republic of Korea.
FAU - Kim, Min-Ho
AU  - Kim MH
AUID- ORCID: 0000-0001-6782-8468
AD  - Epi Biotech Co., Ltd., Incheon 21983, Republic of Korea.
FAU - Park, Sang-Gyu
AU  - Park SG
AUID- ORCID: 0000-0002-4870-2242
AD  - College of Pharmacy, Ajou University, Suwon 16499, Republic of Korea.
FAU - Kim, Won-Serk
AU  - Kim WS
AD  - Department of Dermatology, School of Medicine, Sungkyunkwan University, Kangbuk 
      Samsung Hospital, Seoul 03181, Republic of Korea.
FAU - Oh, Sang-Ho
AU  - Oh SH
AD  - Department of Dermatology and Cutaneous Biology Research Institute, Severance 
      Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
FAU - Sung, Jong-Hyuk
AU  - Sung JH
AD  - Epi Biotech Co., Ltd., Incheon 21983, Republic of Korea.
LA  - eng
GR  - HN22C0027/Korea Drug Development Fund/
PT  - Journal Article
DEP - 20240130
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Androgens)
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Chemokine CXCL12)
RN  - Diffuse alopecia
SB  - IM
MH  - Animals
MH  - Mice
MH  - Alopecia/metabolism
MH  - *Alopecia Areata/drug therapy/metabolism
MH  - Androgens/metabolism
MH  - *Antibodies, Neutralizing/pharmacology/metabolism
MH  - Hair
MH  - Hair Follicle/metabolism
MH  - Skin/metabolism
MH  - Chemokine CXCL12/immunology
PMC - PMC10855715
OTO - NOTNLM
OT  - CXCL12
OT  - alopecia areata
OT  - androgenic alopecia
OT  - dermal fibroblasts
OT  - neutralizing antibody
COIS- Authors Mei Zheng and Min-Ho Kim were employed by the Epi Biotech. Co., Ltd. The 
      remaining authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2024/02/10 10:45
MHDA- 2024/02/10 10:46
PMCR- 2024/01/30
CRDT- 2024/02/10 01:12
PHST- 2023/12/21 00:00 [received]
PHST- 2024/01/19 00:00 [revised]
PHST- 2024/01/25 00:00 [accepted]
PHST- 2024/02/10 10:46 [medline]
PHST- 2024/02/10 10:45 [pubmed]
PHST- 2024/02/10 01:12 [entrez]
PHST- 2024/01/30 00:00 [pmc-release]
AID - ijms25031705 [pii]
AID - ijms-25-01705 [pii]
AID - 10.3390/ijms25031705 [doi]
PST - epublish
SO  - Int J Mol Sci. 2024 Jan 30;25(3):1705. doi: 10.3390/ijms25031705.