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MicroRNA Expression Profiles of Human iPS Cells, Retinal Pigment Epithelium Derived From iPS, and Fetal Retinal Pigment Epithelium
Published on: June 24, 2014
Integrated microRNA/mRNA expression profiling of the skin of psoriasis patients
Denis Delić1, Kerstin Wolk2, Ramona Schmid1
1Translational Medicine & Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
Background:
Psoriasis is a chronic inflammatory disease characterized by demarcated, raised, and scaling skin lesions. It often serves as a model for immune-mediated disorders. Gene expression profiling of affected skin has allowed insights into psoriasis pathogenesis. However, the mechanisms leading to specific mRNA expression alterations in psoriasis are barely understood.
Objectives:
To perform integrated microRNA-mRNA expression studies of non-lesional, peri-lesional, and lesional skin from psoriasis patients.
Methods:
Cutaneous microRNA and mRNA expression profiles of 14 patients using Nanostring nCounter-technology and RNA sequencing as well as in vitro keratinocyte stimulation and qPCR studies.
Results:
Only 3.5 % of microRNAs manifested a robust gradual expression trend from non-lesional to paired lesional skin, with 61 % being upregulated and 39 % being downregulated. Relevance of these microRNA regulations was supported by their inverse association with 57 % of the mRNA species found to be regulated during psoriatic lesion development. Many of the involved mRNAs were downregulated and functionally related to keratinocyte metabolism, barrier function, and neuronal signaling, and were already regulated in peri-lesional skin. An integrated correlation analysis revealed a robust interaction for 134 microRNAs/mRNAs pairs. In vitro keratinocyte studies of selected microRNAs/mRNAs revealed regulations of all analyzed microRNAs in a psoriasis-like manner by IL-17A/TNF-α (e.g. hsa-miR-23a-3p), IFN-γ (e.g. hsa-miR-106a-5p/miR-17-5p), or IL-24 (e.g. hsa-miR-203a-3p). Moreover, most of their predicted target mRNAs (e.g. ID4, EPHB2) were respectively altered by the same cytokines.
Conclusion:
Our study suggests that, during development of psoriatic lesions, defined aspects of psoriasis pathogenesis are regulated by the action of microRNAs.
Insights
MicroRNAs play a key role in psoriasis pathogenesis, regulating mRNA expression in skin lesions. This study reveals specific microRNA-mRNA interactions involved in psoriatic lesion development.
Area of Science:
- Dermatology and immunology
- Molecular biology
- Gene expression analysis
Background:
- Psoriasis is a chronic inflammatory skin disease with characteristic lesions.
- Understanding psoriasis pathogenesis is crucial for developing effective treatments.
- Gene expression profiling offers insights into disease mechanisms, but regulatory pathways remain unclear.
Purpose of the Study:
- To investigate the integrated roles of microRNAs (miRNAs) and messenger RNAs (mRNAs) in psoriasis.
- To analyze miRNA and mRNA expression profiles in non-lesional, peri-lesional, and lesional skin of psoriasis patients.
Main Methods:
- Utilized Nanostring nCounter technology and RNA sequencing for cutaneous miRNA and mRNA profiling in 14 patients.
- Conducted in vitro keratinocyte stimulation and quantitative PCR (qPCR) studies.
- Performed integrated correlation analysis to identify miRNA-mRNA interactions.
Main Results:
- Identified a subset of miRNAs with gradual expression changes from non-lesional to lesional skin, with most upregulated.
- Found inverse associations between regulated miRNAs and 57% of mRNAs involved in psoriatic lesion development.
- Observed downregulation of mRNAs related to keratinocyte metabolism, barrier function, and neuronal signaling, already altered in peri-lesional skin.
- Revealed robust interactions for 134 miRNA/mRNA pairs and confirmed cytokine-mediated regulation of selected miRNAs and their target mRNAs in vitro.
Conclusions:
- MicroRNAs are suggested to regulate key aspects of psoriasis pathogenesis during lesion development.
- Specific miRNA-mRNA interactions are implicated in the molecular mechanisms underlying psoriatic skin changes.
- Findings highlight the potential of targeting miRNA pathways for psoriasis treatment.
