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Mesenchymal Stem Cells Alleviate Psoriasis by Regulating the PSPH-PINK1-Parkin-NLRP3 Pathway in HaCaT Keratinocytes via Serine Metabolism

Authors: Qing Lin; Yunfei Ji; Bin Yang; Rongjia Zhu; Ping Song; Robert Chunhua Zhao

DOI: 10.1186/s13287-026-04964-zStatus: Verified Academic AccessLicense: CC-BY 4.0 Academic Open Access

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Key Findings in This Report

• • MSCs significantly improved IMQ-induced psoriasis skin lesions in mice, reducing inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) and chemokines (MCP-1, CCL7, CCL20, CCL27) in skin lesions and M5-induced HaCaT cells, with statistical significance (P<0.05 to P<0.001). • • MSCs restored skin barrier by upregulating claudin-1 expression in vivo, and normalized keratinocyte differentiation markers (increased KRT1, decreased KRT6) both in vivo and in vitro, indicating functional recovery of epidermal differentiation. • • Amino acid metabolomics showed MSCs improved serine metabolism in mouse skin, upregulating key enzyme PSPH; knockdown of PSPH reversed MSCs' therapeutic effects in vitro, confirming PSPH as a critical mediator. • • MSCs activated PINK1-Parkin mitophagy pathway, with elevated PINK1, Parkin, p-Parkin, Beclin-1, and LC3B-II/I ratio, and reduced P62 (n=3, P<0.05 to P<0.001), leading to suppression of NLRP3 inflammasome and keratinocyte hyperproliferation.