Transcriptomics,Genomics

Dataset Information

19

Wound Healing Protects Against Chemotherapy-induced Alopecia in Young Rats via Up-regulating Interleukin-1β-mediated Signaling


ABSTRACT: 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). Overall design: Gene expression in rat acute wound: A 3-mm incisional wound was made on the dorsum of Long-Evans rat pups 3 days after birth. Thirty-six hours later, skin specimens were collected from the wound sites (wound) and corresponding sites of unwounded rat pups (control). Total RNA was extracted with TriZol Reagent (Life Technologies, Grand Island, NY) and purified with the RNeasy micro kit (Qiagen), and sent to Ocean Ridge Biosciences (ORB, Palm Beach Gardens, FL) for microarray analysis using the Rat MI-Ready array from Microarrays Inc.

INSTRUMENT(S): RN1100_Rat_MI_ReadyArray

SUBMITTER: Tongyu Wikramanayake   

PROVIDER: GSE98105 | GEO | 2017-06-29

SECONDARY ACCESSION(S): PRJNA384003

REPOSITORIES: GEO

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Publications

Wound healing protects against chemotherapy-induced alopecia in young rats via up-regulating interleukin-1β-mediated signaling.

Stojadinovic Olivera O   Wikramanayake Tongyu C TC   Villasante Fricke Alexandra C AC   Yin Natalie C NC   Liang Liang L   Hinde Eleanor E   Escandon Julia J   Tomic-Canic Marjana M   Ansell David M DM   Paus Ralf R   Jimenez Joaquin J JJ  

Heliyon 20170530 5


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 cause  ...[more]

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