國家衛生研究院 NHRI:Item 3990099045/15611
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    题名: Profibrotic subsets of SPP1(+) macrophages and POSTN(+) fibroblasts contribute to fibrotic scarring in acne keloidalis
    作者: Hong, YK;Hwang, DY;Yang, CC;Cheng, SM;Chen, PC;Aala, WJ;H, ICH;Evans, ST;Onoufriadis, A;Liu, SL;Lin, YC;Chang, YH;Lo, TK;Hung, KS;Lee, YC;Tang, MJ;Lu, KQ;McGrath, JA;Hsu, CK
    贡献者: National Institute of Cancer Research
    摘要: Acne keloidalis (AK) is a primary scarring alopecia characterized by longstanding inflammation in the scalp causing keloid-like scar formation and hair loss. Histologically, AK is characterized by mixed leukocytic infiltrates in the acute stage followed by a granulomatous reaction and extensive fibrosis in the later stages. To further explore its pathogenesis, bulk RNA-sequencing, single-cell RNA-sequencing, and spatial transcriptomics were applied to occipital scalp biopsy specimens of lesional and adjacent non-lesional skin in patients with clinically active disease. Unbiased clustering revealed 19 distinct cell populations, including two notable populations, POSTN(+) fibroblasts with enriched extracellular matrix signatures and SPP1(+) myeloid cells with a M2 macrophage phenotype. Cell communication analyses indicated that fibroblasts and myeloid cells communicated by SPP1 signaling networks in lesional skin. A reverse transcriptomics in-silico approach identified corticosteroids as possessing the capability to reverse the gene expression signatures of SPP1(+) myeloid cells and POSTN(+) fibroblasts. Intralesional corticosteroid injection greatly reduced SPP1 and POSTN gene expression, as well as AK disease activity. Spatial transcriptomics and immunofluorescence staining verified micro-anatomic specificity of SPP1(+) myeloid cells and POSTN(+) fibroblasts with disease activity. In summary, the communication between POSTN(+) fibroblasts and SPP1(+) myeloid cells by SPP1 axis may contribute to the pathogenesis of AK.
    日期: 2024-07
    關聯: Journal of Investigative Dermatology. 2024 Jul;144(7):1491-1504.e10.
    Link to: http://dx.doi.org/10.1016/j.jid.2023.12.014
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-202X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:001295940700001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85185781969
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