miR-34a Mediates IL-23/IL-17 Immune Inflammation and Promotes Cell Proliferation in HaCaT Cells by Targeting...

Area of Science:

• Dermatology
• Immunology
• Molecular Biology

Background:

• Psoriasis is a common immune-mediated skin disorder.
• MicroRNA-34a (miR-34a) is implicated in immune-inflammatory regulation and shows abnormal expression in psoriasis models.
• The precise role of miR-34a in psoriasis pathogenesis remains unclear.

Purpose of the Study:

• To investigate the role of miR-34a in psoriasis pathogenesis.
• To elucidate the molecular mechanisms underlying miR-34a's function in psoriasis.
• To evaluate the therapeutic potential of targeting miR-34a in psoriasis models.

Main Methods:

• Established an in vitro psoriasis model using HaCaT cells co-stimulated with inflammatory cytokines.
• Utilized qPCR, ELISA, CCK-8, EdU staining, and Western blot to analyze miR-34a expression, cytokine levels, cell proliferation, and protein expression.
• Employed dual-luciferase reporter gene assays and RNA immunoprecipitation (RIP) to confirm the interaction between miR-34a and SIRT1.
• Induced an imiquimod (IMQ)-mediated psoriasis model in mice for in vivo validation.

Main Results:

• miR-34a was significantly upregulated in HaCaT cells and mouse skin models of psoriasis.
• Psoriasis models exhibited elevated levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-17, IL-23) and increased HaCaT cell proliferation.
• miR-34a inhibition reversed these changes, reducing inflammation and proliferation.
• M5 treatment decreased SIRT1 and increased NLRP3 inflammasome components (NLRP3, ASC, Caspase-1).
• miR-34a directly targets SIRT1, establishing a negative feedback loop.
• SIRT1 overexpression suppressed NLRP3 and inflammation, while NLRP3 overexpression exacerbated it.
• In vivo, miR-34a inhibition ameliorated IMQ-induced psoriasis phenotypes and skin pathology.

Conclusions:

• miR-34a plays a critical role in promoting psoriasis by mediating the IL-23/IL-17 immune-inflammatory response and HaCaT cell proliferation.
• The mechanism involves the regulation of the SIRT1/NLRP3 pathway.
• Targeting miR-34a presents a potential therapeutic strategy for psoriasis.