Title | Human Umbilical Cord-Derived Mesenchymal Stem Cells Alleviate Psoriasis Through TNF-a/NF-?B/MMP13 Pathway |
Authors | Ren, Xuanyao Zhong, Weilong Li, Wenting Tang, Mindan Zhang, Kaoyuan Zhou, Fenli Shi, Xin Wu, Jun Yu, Bo Huang, Cong Chen, Xiaofan Zhang, Wei |
Affiliation | Hong Kong Univ Sci & Technol, Shenzhen Peking Univ, Biomed Res Inst, Med Ctr,Shenzhen Key Lab Translat Med Dermatol, Shenzhen 518036, Guangdong, Peoples R China Peking Univ, Shenzhen Hosp, Dept Dermatol, 1120,Lianhua Rd, Shenzhen 518036, Peoples R China Peking Univ, Shenzhen Hosp, Dept Neurol, 1120,Lianhua Rd, Shenzhen 518036, Peoples R China Shenzhen Bay Lab, Greater Bay Biomed Innoctr, Shenzhen, Guangdong, Peoples R China |
Keywords | MATRIX METALLOPROTEINASES TNF DIFFERENTIATION PATHOGENESIS MIGRATION |
Issue Date | Feb-2023 |
Publisher | INFLAMMATION |
Abstract | Psoriasis is a chronic, immune-mediated disease that affects 2-3% of the global population. Recently, mesenchymal stem cells (MSCs) have been used to alleviate psoriasis. However, the therapeutic mechanisms of MSCs remain unclear. Matrix metalloproteinase-13 (MMP13), a member of the MMPs family, is the key enzyme in the cleavage of type II collagen and plays a pivotal role in extracellular matrix (ECM) remodeling. Here, it was found that Mmp13 was upregulated in the skin lesions of an imiquimod-induced mouse model, which was downregulated after intravenous infusion of human umbilical cord MSCs (hUC-MSCs). Knockdown of MMP13 inhibited the proliferation of keratinocytes and arrested the cell cycle in G1 stage. In addition, hUC-MSCs were co-cultured with THP-1 or PMA-stimulated THP-1 directly in vitro to simulate the fate of systematically infused hUC-MSCs. The level of TNF-alpha was decreased in the supernatant of co-cultured hUC-MSCs and THP-1 or PMA-stimulated THP-1. Moreover, it was identified that TNF-alpha upregulated MMP13 through the NF-kappa B pathway in keratinocytes. In conclusion, we propose that systematically infused hUC-MSCs exert a therapeutic effect on psoriasis through the TNF-alpha/NF-kappa B/MMP13 pathway. |
URI | http://hdl.handle.net/20.500.11897/671400 |
ISSN | 0360-3997 |
DOI | 10.1007/s10753-023-01785-7 |
Indexed | SCI(E) |
Appears in Collections: | 化学生物学与生物技术学院 深圳医院 |