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Role of human dural fibroblasts in the angiogenic responses of human endothelial cells: an in vitro dural model for EDAS

ABSTRACT: To determine whether dural fibroblasts (DuF) under IL-1β-mediated wound conditions, release pro-angiogenic factors, and promote angiogenic properties in human endothelial cells (ECs). DuF were stimulated by pro-inflammatory cytokines interleukin (IL)-1β, and transcriptome sequencing was then used to identify the differentially expressed genes in the DuF with/without IL-1β stimulation (DuFCon/DuFIL1b)

ORGANISM(S): Homo sapiens

PROVIDER: GSE224999 | GEO | 2023/02/15

REPOSITORIES: GEO

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Project description:Wound healing is a complex process regulated by various cell types and a plethora of mediators. While interactions between wounded skin and the hair follicles (HFs) could induce HF neogenesis or promote wound healing, it remains unknown whether the wound healing-associated signaling milieu can be manipulated to protect against alopecia, such as chemotherapy-induced alopecia (CIA). Utilizing a well-established neonatal rat model of CIA, we show here that skin wounding protects from alopecia caused by several clinically relevant chemotherapeutic regimens, and that protection is dependent on the time of wounding and hair cycle stage. Gene expression profiling unveiled a significant increase in interleukin-1 beta (IL-1β) mediated signaling by skin wounding. Subsequently, we showed that IL-1β is sufficient and indispensable for mediating the CIA-protective effect. Administration of IL-1β alone to unwounded rats exhibited local CIA protection while IL-1β neutralization abrogated CIA protection by wounding. Mechanistically, IL-1β retarded postnatal HF morphogenesis, making HFs at the wound sites or IL-1β treated areas damage-resistant while the rats developed total alopecia elsewhere. We conclude that wound healing switches the cutaneous cytokine milieu to an IL-1β-dominated state thus retarding HF growth progression and rendering the HFs resistant to chemotherapy agents. In the future, manipulation of HF progression through interfering with the IL-1β signaling milieu may provide therapeutic benefits to a variety of conditions, from prevention of CIA to inhibition of hair growth and treatment of hirsutism. In this experiment, we used the Rat MI-Ready array comprised of over 34,000 transcript probes for gene and alternative splice products in ENSEMBL release 37 to profile gene expression changes during acute wound healing in rat skin. 16,198 Selected rat probes were above threshold in at least one group. 3,239 significant genes were found (FDR < 0.1).

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Role of human dural fibroblasts in the angiogenic responses of human endothelial cells: an in vitro dural model for EDAS

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