JAM-A facilitates hair follicle regeneration in alopecia areata through functioning as ceRNA to protect VCAN expression in dermal papilla cells

Minjuan Wu; Chen Xu; Junfeng Jiang; Sha Xu; Jun Xiong; Xiaoming Fan; Kaihong Ji; Yunpeng Zhao; Haitao Ni; Yue Wang; Houqi Liu; Zhaofan Xia

doi:10.1093/pcmedi/pbac020

JAM-A facilitates hair follicle regeneration in alopecia areata through functioning as ceRNA to protect VCAN expression in dermal papilla cells

Precis Clin Med. 2022 Aug 17;5(3):pbac020. doi: 10.1093/pcmedi/pbac020. eCollection 2022 Sep.

Authors

Minjuan Wu^{1

2}, Chen Xu^{1

3}, Junfeng Jiang¹, Sha Xu¹, Jun Xiong¹, Xiaoming Fan², Kaihong Ji¹, Yunpeng Zhao¹, Haitao Ni¹, Yue Wang^{1

4}, Houqi Liu¹, Zhaofan Xia²

Affiliations

¹ Department of Histology and Embryology, Naval Medical University, Shanghai 200433, China.
² Burns Institute of People's Liberation Army, Changhai Hospital, Naval Medical University, Shanghai 200433, China.
³ Spine Center, Department of Orthopedics, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
⁴ Translational Medicine Center, Naval Medical University, Shanghai 200433, China.

Abstract

The dermal papilla cells in hair follicles function as critical regulators of hair growth. In particular, alopecia areata (AA) is closely related to the malfunctioning of the human dermal papilla cells (hDPCs). Thus, identifying the regulatory mechanism of hDPCs is important in inducing hair follicle (HF) regeneration in AA patients. Recently, growing evidence has indicated that 3' untranslated regions (3' UTR) of key genes may participate in the regulatory circuitry underlying cell differentiation and diseases through a so-called competing endogenous mechanism, but none have been reported in HF regeneration. Here, we demonstrate that the 3' UTR of junctional adhesion molecule A (JAM-A) could act as an essential competing endogenous RNA to maintain hDPCs function and promote HF regeneration in AA. We showed that the 3' UTR of JAM-A shares many microRNA (miRNA) response elements, especially miR-221-3p, with versican (VCAN) mRNA, and JAM-A 3' UTR could directly modulate the miRNA-mediated suppression of VCAN in self-renewing hDPCs. Furthermore, upregulated VCAN can in turn promote the expression level of JAM-A. Overall, we propose that JAM-A 3' UTR forms a feedback loop with VCAN and miR-221-3p to regulate hDPC maintenance, proliferation, and differentiation, which may lead to developing new therapies for hair loss.

Keywords: JAM-A 3′ UTR; VCAN; alopecia areata; dermal papilla cells; miR-221-3p.