Interleukin-6 Null Mice Paradoxically Display Increased STAT3 Activity and Wound-Induced Hair Neogenesis

Nelson, Amanda M.; Katseff, Adiya S.; Resnik, Sydney R.; Ratliff, Tabetha S.; Zhu, Amadeus S.; Garza, Luis A.

doi:10.1016/j.jid.2015.12.043

Cited by 18 publications

(12 citation statements)

References 9 publications

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“…We found the cycle-related expression of RIPK-1 and RIPK-3 in mouse and human HF cells: It was found in the anagen HFs and absent in telogen ones ( Morgun et al, 2020 ). As it was described above, hair growth may be promoted via dsRNA/TLR3/IL-6/STAT3 pathway ( Nelson et al, 2015 , 2016a _A; Nelson et al, 2016b _B). Based on Moriwaki data obtained in a mouse model of colitis, as well as in an experiment on bone-marrow-derived dendritic cells, it can be concluded that after LPS-induced stimulation of TLR4, RIPK-3 participates in the activation of the NF-κβ pathway, which leads to interleukin expression and STAT3 phosphorylation ( Moriwaki et al, 2014 ).…”

Section: Discussionmentioning

confidence: 94%

“…Nelson and colleagues found that activation of TLR3 by polyriboinosinic-polyribocytidylic acid (polyI: C), simulating the viral dsRNA in keratinocyte cell culture ( Takada et al, 2017 ), causes a loss of Keratin1 and filaggrin (markers of differentiated keratinocytes) and an increase in the expression of Lgr5 and Lgr6 HF progenitor markers as well as Krt15 ( Nelson et al, 2015 ). Besides, the participation of IL-6/STAT3 pathway in the acquisition of stem status is indirectly confirmed by the fact that STAT3 phosphorylation under the influence of IL-6 family members IL-11 and Oncostatin M (OSM) contributes to WIHN ( Nelson et al, 2016b _B). There is experimental evidence that TA isoforms of stem/progenitor marker p63, which expression is affected by IL-6/STAT3, are involved both in the inhibition of keratinocytes ability to differentiate and in the stimulation of WIHN ( Nelson et al, 2016a _A).…”

Section: Episc Plasticity During Wound Healing Under the Influence Ofmentioning

confidence: 94%

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Epidermal Stem Cells in Hair Follicle Cycling and Skin Regeneration: A View From the Perspective of Inflammation

Morgun

Vorotelyak

2020

Front. Cell Dev. Biol.

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Section: Discussionmentioning

confidence: 94%

Section: Episc Plasticity During Wound Healing Under the Influence Ofmentioning

confidence: 94%

Epidermal Stem Cells in Hair Follicle Cycling and Skin Regeneration: A View From the Perspective of Inflammation

Morgun

Vorotelyak

2020

Front. Cell Dev. Biol.

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“…STAT3 activation is a prerequisite for the early anagen of hair follicles ( Sano et al, 2008 ) and keratinocytes-specific STAT3 knockout mice exhibited impaired hair cycle ( Sano et al, 1999 ). Additionally, STAT3 can maintain keratinocyte stem/progenitor cell homeostasis via facilitating the maturation of the bulge region in mouse hair follicle development ( Sano et al, 2000 , 2008 ; Rao et al, 2015 ; Shibata et al, 2015 ; Nelson et al, 2016 ). FST promotes hair follicle development via binding activins and preventing the activation of activin receptors ( Mcdowall et al, 2008 ).…”

Section: Discussionmentioning

confidence: 99%

STAT3 Partly Inhibits Cell Proliferation via Direct Negative Regulation of FST Gene Expression

et al. 2021

Front. Genet.

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Follistatin (FST) is a secretory glycoprotein and belongs to the TGF-β superfamily. Previously, we found that two single nucleotide polymorphisms (SNPs) of sheep FST gene were significantly associated with wool quality traits in Chinese Merino sheep (Junken type), indicating that FST is involved in the regulation of hair follicle development and hair trait formation. The transcription regulation of human and mouse FST genes has been widely investigated, and many transcription factors have been identified to regulate FST gene. However, to date, the transcriptional regulation of sheep FST is largely unknown. In the present study, genome walking was used to close the genomic gap upstream of the sheep genomic FST gene and to obtain the FST gene promoter sequence. Transcription factor binding site analysis showed sheep FST promoter region contained a conserved putative binding site for signal transducer and activator of transcription 3 (STAT3), located at nucleotides −423 to −416 relative to the first nucleotide (A, +1) of the initiation codon (ATG) of sheep FST gene. The dual-luciferase reporter assay demonstrated that STAT3 inhibited the FST promoter activity and that the mutation of the putative STAT3 binding site attenuated the inhibitory effect of STAT3 on the FST promoter activity. Additionally, chromatin immunoprecipitation assay (ChIP) exhibited that STAT3 is directly bound to the FST promoter. Cell proliferation assay displayed that FST and STAT3 played opposite roles in cell proliferation. Overexpression of sheep FST significantly promoted the proliferation of sheep fetal fibroblasts (SFFs) and human keratinocyte (HaCaT) cells, and overexpression of sheep STAT3 displayed opposite results, which was accompanied by a significantly reduced expression of FST gene (P < 0.05). Taken together, STAT3 directly negatively regulates sheep FST gene and depresses cell proliferation. Our findings may contribute to understanding molecular mechanisms that underlie hair follicle development and morphogenesis.

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“…Spatial plots showed the preferentially aggregation of Il6 and Inhba in large wound margin and center (co-localized with HFSC, PF as well as PIM, Mono, T cells). The essential role of activin [43, 44] and Il6 [12] pathway in HF regeneration has been reported. Our result illustrated that immune cell especially PIM, Mono and T cells may modulate the states of PF, HFP and HFSC through signaling pathways such as IL-6 and activin.…”

Section: Introductionmentioning

confidence: 99%

“…Intriguingly, some capacity for "half-functional" regeneration has been demonstrated in large (larger than 1 cm 2 ) full thickness wound of adult mice skin in WIHN model [5,6] . It has been inferred that immune cells 4 / 83 (mainly macrophages, T cells ) might be the key orchestrators of wound healing that selectively promoting scarring [7][8][9] or regenerative WIHN [10][11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

Tracing immune cells around biomaterials with spatial anchors during large-scale wound regeneration

YANG¹,

Chu²,

Hu³

et al. 2022

Preprint

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Fibrotic scar is one of the primary impediments to severe skin wound healing, characterized by excessive deposition of extracellular matrix (ECM) devoid of skin appendages including hair follicle (HF). Intriguingly, functional hair follicles can regenerate specifically in the large wound center of adult mice, termed wound-induced hair neogenesis (WIHN). Single-cell RNA sequencing (scRNA-Seq) comparisons of small and large wound showed increased activation of adaptive immune systems which might associated with predominance of papillary fibroblast (PF) in large wound. Integration the gene expression profiles of spatial transcriptomic (ST) and scRNA-Seq highlighted a pro-regenerative immune niche, composing of T cells, pro-inflammatory macrophage (PIM) and monocyte surrounding the migrating hair follicle stem cell (HFSC) and PF in large wound center. Local pro-regenerative immune response predicted by Cellchat provided potential therapeutic target for the further HF regeneration. Aligned electrospinning scaffolds were previously shown to accelerate small wound healing with the immunomodulatory effect of T cells and macrophages. Here we showed that wound recapitulated normal skin architecture with the implantation of scaffold despite wound size. Enlarged distribution of the pro-regenerative immune niche co-localization with PF may account for the well-proportioned de novo HF in scaffold-implanted group. Collectively, our study illustrated that manipulating the adaptive immune system may stimulate de novo HF regeneration via local cell-cell interactions.

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Interleukin-6 Null Mice Paradoxically Display Increased STAT3 Activity and Wound-Induced Hair Neogenesis

Cited by 18 publications

References 9 publications

Epidermal Stem Cells in Hair Follicle Cycling and Skin Regeneration: A View From the Perspective of Inflammation

Epidermal Stem Cells in Hair Follicle Cycling and Skin Regeneration: A View From the Perspective of Inflammation

STAT3 Partly Inhibits Cell Proliferation via Direct Negative Regulation of FST Gene Expression

Tracing immune cells around biomaterials with spatial anchors during large-scale wound regeneration

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