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Related articles to: KLK-L2 antibody
- The acidic microenvironment of the stratum corneum is crucial for epidermal desquamation and barrier homeostasis, yet the primary proton sensor that triggers this process remains unknown. Here, we report that the proton-activated chloride channel PACC1 is essential for acid-induced upregulation of kallikreins (KLKs) and desmosomal degradation, two key steps in skin exfoliation. Functional and protein expression analyses revealed that PACC1 is the predominant acid-sensitive ion channel in keratinocytes. Proton-mediated PACC1 activation evokes chloride efflux and initiates a signaling cascade via the c-Jun N-terminal Kinase/AP-1 (JNK/AP-1) pathway. This cascade significantly enhances the expression and secretion of KLKs (KLK5/7), thereby facilitating desquamation through corneodesmosomal degradation. Notably, acid-induced KLK upregulation was abolished by PACC1 knockdown, knockout, or mutants that are deficient in proton sensing. This effect was also observed with pharmacological channel inhibition and was specifically restored by reconstitution with functional PACC1. These findings establish PACC1 as the core sensor that converts epidermal acidification into a desquamation signal, providing a mechanistic foundation for developing targeted therapeutic and cosmetic strategies that modulate skin barrier function. - Source: PubMed
Publication date: 2026/03/31
Xia KeyuLiu XiangjianWu JiajingHu JunyanCheng XufengMi TingyanGao BominMo XiaoyiLu XutengCao FengXie ChangCao JianPernodet NadineHe GuangwenZhou HuanjunYao Jing - - Source: PubMed
Publication date: 2026/03/22
Wang ZheDing LongkunZhu QingweiOu QingjianWang QiXie YingLi LiLiu XuanNi ChenghaoWang YufengLiu YongheYu LitingCai JiahuiGao Lu - This study aimed to systematically elucidate, for the first time, the therapeutic mechanism of Cuochuangling pills, (CCLP), a clinical herbal formulation for rosacea, through an innovative integrated approach combining network pharmacology, multi-method bioinformatics, and experimental validation. - Source: PubMed
Publication date: 2026/03/04
Shen XiaoyingLiu DonghuZhu ZhengjinZhao ShengjieYan XiaoningLi Meihong - Rosacea is a chronic inflammatory skin disease, with LL-37 driving inflammation. Inhibiting serine protease kallikrein-5 (KLK5) overactivity can reduce LL-37 production, thereby relieving this inflammation. Lithospermic acid (LA), a plant-derived synthetic phenolic carboxylic acid, is known for its potent anti-inflammatory and antioxidant effects. However, its effects on rosacea remain unelucidated. This study aimed to investigate the KLK5-inhibiting activity of LA to assess its therapeutic efficacy in rosacea management, along with identifying its underlying mechanisms. - Source: PubMed
Publication date: 2026/01/26
Xu JingangWang XinyuChen ManyuXu BoyaZhang TingtingZhang YaoXu YueyeGuo JunjieXu JingyunLi YuanyuanZhao JinhongZhou Hongming - Secondary hair follicle stem cells (HFSCs) are essential for cashmere fiber regeneration, yet the molecular mechanisms governing their activation and lineage progression remain poorly understood. Here, we identify S100a4 as a key regulator of secondary HFSCs in cashmere goat. expression peaks during anagen and is markedly enriched in secondary HFSCs relative to hair matrix cells (HMCs), suggesting a role in initiating follicle regeneration. Functional assays show that promotes HFSCs into a dynamically regulated state that activates stem cell competence while facilitating differentiation, with overexpression upregulating epidermal and follicular differentiation markers (, , , ), as well as pluripotency genes (, ), while knockdown suppresses these programs. Proteomic analysis further reveals direct interactions between S100A4 and keratins critical for hair follicle and epidermal development (KRT5, KRT14, KRT8, KRT18), suggesting a structural and regulatory interface through which S100A4 modulates HFSC fate. Collectively, these results establish S100a4 as a central modulator of secondary HFSC function and provide mechanistic insight into the molecular control of hair follicle regeneration, with potential implications for improving cashmere fiber production. - Source: PubMed
Publication date: 2026/01/15
Liang XinyueLiu BohanWang JiayiLiu YanleiWei YipingYu HongjiZhang JunpengZhang ShuyiXue Huiling