Abstract
Specific deletion of suppressor of cytokine signaling 3 (Socs3) in keratinocytes can cause severe skin inflammation with infiltration of immune cells. The molecular mechanisms and key regulatory pathways involved in these processes remain elusive. To investigate the role of Socs3 in keratinocytes, we generated and analyzed global RNA-Seq profiles from Socs3 conditional knockout (cKO) mice of two different ages (2 and 10 weeks). Over 400 genes were significantly regulated at both time points. Samples from 2-week-old mice exhibited down-regulation of genes involved in keratin-related functions and up-regulation of genes involved in lipid metabolism. At week 10, multiple chemokine and cytokine genes were up-regulated. Functional annotation revealed that the genes differentially expressed in the 2-week-old mice play roles in keratinization, keratinocyte differentiation, and epidermal cell differentiation. By contrast, differentially expressed genes in the 10-week-old animals are involved in acute immune-related functions. A group of activator protein-1–related genes were highly up-regulated in Socs3 cKO mice of both ages. This observation was validated using qRT-PCR by SOCS3-depleted human keratinocyte–derived HaCaT cells. Our results suggest that, in addition to participating in immune-mediated pathways, SOCS3 also plays important roles in skin barrier homeostasis.
Highlights
Skin is an essential organ that consists of two major layers, the epidermis and dermis
To investigate the global molecular perturbations associated with deletion of Socs[3] in keratinocytes, we compared gene expression between wild-type (C57BL/6 mice) and Socs[3] conditional knockout (Socs[3] cKO) mice at two different ages, 2 and 10 weeks
The results revealed that a series of molecular perturbations in the epidermis began at 2 weeks that led to a skin disease–like phenotype[13], indicating that Socs[3] plays an important role in skin barrier homeostasis
Summary
Skin is an essential organ that consists of two major layers, the epidermis and dermis. Cytokines are essential intercellular mediators of immune signals regulated by SOCS (Suppressor of Cytokine Signaling) family proteins, which communicate extensively with various cellular and molecular responses via the JAK–STAT (Janus kinase–signal transducer and activator of transcription) pathway and dynamically regulate tissue hemostasis[3,4,5] These systems are robust, perturbation of any of their components can lead to a variety of diseases, including allergy, autoimmune skin diseases, inflammation, and cancers[5,6,7,8,9,10,11]. Our findings provide new molecular insights into how perturbed epidermal homeostasis contributes to the development of skin diseases
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
