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CRF1 receptor splicing in epidermal keratinocytes: potential biological role and environmental regulations.

ABSTRACT: Corticotropin releasing factor receptor type 1 (CRF1), a coordinator of the body responses to stress, is also expressed in human skin, where it undergoes alternative splicing. Since the epidermis is continuously exposed to the environmental stress, human keratinocytes were chosen to study the biological role of CRF1 alternative splicing. The expression pattern of CRF1 isoforms depended on cell density, presence or absence of serum, and exposure to ultraviolet irradiation (UVR). Only two isoforms alpha and c were predominantly localized to the cell membrane, with only CRF1alpha being efficient in stimulating cAMP responding element (CRE). CRF1d, f and g had intracellular localization, showing no or very low (g) activation of CRE. The co-expression of CRF1alpha with d, f or g resulted in intracellular retention of both isoforms suggesting dimerization confirmed by detection of high molecular weight complexes. The soluble isoforms e and h were diffusely distributed in the cytoplasm or localized to the ER, respectively, and additionally found in culture medium. These findings suggest that alternatively spliced CRF1 isoforms can interact and modify CRF1alpha subcellular localization, thus affecting its activity. We suggest that alternative splicing of CRF1 may play an important role in the regulation of skin cell phenotype with potential implications in pathology.

SUBMITTER: Zmijewski MA

PROVIDER: S-EPMC2612097 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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CRF1 receptor splicing in epidermal keratinocytes: potential biological role and environmental regulations.

Zmijewski Michal A MA Slominski Andrzej T AT

Journal of cellular physiology 20090301 3

Corticotropin releasing factor receptor type 1 (CRF1), a coordinator of the body responses to stress, is also expressed in human skin, where it undergoes alternative splicing. Since the epidermis is continuously exposed to the environmental stress, human keratinocytes were chosen to study the biological role of CRF1 alternative splicing. The expression pattern of CRF1 isoforms depended on cell density, presence or absence of serum, and exposure to ultraviolet irradiation (UVR). Only two isoforms ...[more]

PMID: 19006179

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Project description:Background/Aims: Mediator complex subunit 1 (MED1) is an important transcriptional co-activator involved in multiple signaling pathways. Previous studies indicated an essential role of MED1 in hair cycling and wound repair through regulating the transcription of mRNAs. Circular RNAs (circRNAs), as a novel class of non-coding RNAs, are involved in various skin biological functions. Our study aimed to investigate the circRNAs expression profile in MED1 epidermal conditional knockout mice (KO), and provide potential candidates as well as the mechanism underlying the circRNAs regulation in both hair follicles and epidermis. Method: Microarray based circRNA expression was determined in MED1 KO mice and wild type mice (WT). The expression level was further confirmed by qRT-PCR. We predicted a possible interaction network of circRNA/microRNA/mRNA by bioinformatics and constructed them with Cytoscape software. Expression of several candidate target mRNAs was verified using qRT-PCR. A TUNEL assay was performed to assess the apoptosis level of MED1 KO and WT skin. Results: Here we identified 109 (34-up, 75-down) distinct circRNAs through microarrays that are differently expressed in MED1 KO mice compared with WT mice (FC > 2 and p-value < 0.05), suggesting a potential role of circRNAs in epidermal regulation. Among these circRNAs, circRNA_004229 was found to decrease significantly after MED1 deletion. The most likely potential targets miRNA for circRNA_004229 include miR-149-5p and miR-207, which possibly further impede the expression of their target mRNA, Tnfrsf19 and Perp, respectively. Apoptosis was suppressed in MED1 KO mice, which implies a potential role of circRNAs in regulating epidermal biological processes including apoptosis. Conclusion: Our study determined the expression profile of circRNAs in MED1 KO skin, and provided hints that circRNA_004229 might be involved in the regulation of keratinocytes in both hair follicles and interfollicular epidermis through a ceRNA mechanism.

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Dataset Information

CRF1 receptor splicing in epidermal keratinocytes: potential biological role and environmental regulations.

Publications

CRF1 receptor splicing in epidermal keratinocytes: potential biological role and environmental regulations.

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