MAPK-related mRNA and miRNA Expression in LPS-treated Keratinocytes: Implications for Psoriasis Inflammation

INTRODUCTION: Psoriasis is a chronic autoimmune disorder characterized by immune dysregulation and excessive keratinocyte proliferation. The mitogen-activated protein kinase (MAPK) signaling pathway plays a key role in driving inflammation in psoriatic skin. METHODS: This study investigated the expression of MAPK-related messenger RNAs (mRNAs) and their regulatory microRNAs (miRNAs) in lipopolysaccharide (LPS)-stimulated human adult low-calcium high-temperature keratinocytes (HaCaT cells). Differential gene and miRNA expression at 2, 8, and 24 hours post-LPS exposure was analyzed using oligonucleotide microarrays. Selected genes were validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and protein levels were assessed using enzyme-linked immunosorbent assay (ELISA). RESULTS: Of 248 MAPK-associated mRNAs, 28 showed significant differential expression. Notably, dual specificity phosphatase 1 (DUSP1), mitogen-activated protein kinase kinase 2 (MAP2K2), MAP2K7, MAP3K2, and MAPK9 were downregulated, while transforming growth factor beta 1 (TGFB1) and interleukin-1 beta (IL1B) were upregulated. Protein-level changes confirmed mRNA findings. Four miRNAs, namely miR-34a, miR-4692a, miR-200-5p, and miR- 1275, exhibited inverse expression trends relative to their predicted targets. DISCUSSION: These results suggest that LPS-induced inflammation causes coordinated dysregulation of MAPK signaling components and their regulatory miRNAs in keratinocytes. The identified miRNAs may serve as potential biomarkers or therapeutic targets for chronic skin inflammation. CONCLUSION: LPS stimulation alters MAPK-related mRNA and protein expression in HaCaT cells and is accompanied by changes in specific regulatory miRNAs. This integrative transcriptomic- proteomic analysis highlights candidate miRNA-mRNA axes relevant to psoriasis pathophysiology and supports further validation in disease-relevant models.