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Abstract Background: Psoriasis is a chronic inflammatory immune mediated disease arising from interaction between genetic risk variants and the environment. Maternally expressed gene3 (MEG3) is a long noncoding RNA (lncRNA) known for gene transcription regulation and inhibiting proliferation. MEG3 competes with microRNA (miRNA-21) influencing cell proliferation and apoptosis balance. Endoplasmic reticulum (ER) stress proteins promote cell survival via unfolded protein response (UPR) influenced by MEG3. Objectives: To detect the possible role of MEG3, miRNA-21 and ER stress proteins in pathogenesis of psoriasis vulgaris. Patients: eighty sex and age matched subjects were included from Dermatology outpatient clinic, Faculty of Medicine, Cairo University, during the stressful covid era between September 2020 and October 2021. The subjects were divided into 2 groups: group (I): included 40 apparently healthy volunteers as healthy skin subjects. group (II): included 40 psoriasis vulgaris patients. Methods: Assessment of human GRP78, ATF6, caspase3, cytokeratin K5 and cytokeratin K14) tissue levels were done by Enzyme Linked Immunosorbent Assay (ELISA). Assessment of long non-coding MEG3 and miRNA -21 expression was done by quantitative real time polymerase chain reaction (qRT-PCR). Results: The expression of miRNA 21 and Keratin-14 were significantly higher among psoriasis patients compared to control group. While expression of MEG3, GRP-78, ATF6, and Caspase-3 were significantly lower among psoriasis patients compared to control group. miRNA 21 and MEG3 were identified as diagnostic markers for psoriasis vulgaris Conclusion: miRNA 21 and MEG3 were identified as diagnostic markers for psoriasis. Expression of miRNA 21 and Keratin-14 was significantly higher among psoriasis patients compared to control. While expression of MEG3, GRP-78, ATF6, and Caspase-3 was significantly lower among psoriasis patients compared to control |