Cell Proliferation最新文献

{"title":"Mechanism of ITGB2 in Osteoclast Differentiation in Osteoarthritis.","authors":"Yang Yang, Rui Sun, Zhibin Lan, Qi Ma, Gang Wu, Di Xue, Zhirong Chen, Yajing Su, Ye Ma, Xiaolei Chen, Jiangbo Yan, Long Ma, Xiaoxin He, Kuanmin Tian, Xiaoyi Ma, Xue Lin, Qunhua Jin","doi":"10.1111/cpr.70107","DOIUrl":"https://doi.org/10.1111/cpr.70107","url":null,"abstract":"<p><p>Transcriptomics studies have identified integrin receptor β2 subunit (ITGB2) as a core gene in osteoarthritis (OA), strongly linked to osteoclast function in the subchondral bone. However, the mechanism through which ITGB2 regulates osteoclast function in OA remains unclear. In this study, we found that ITGB2 was negatively correlated with ITGB1 in the human subchondral bone. Proteomic analysis indicated that integrin binding is crucial in OA subchondral bone, with ITGB2 identified as a significantly upregulated protein in OA. In vitro experiments using immunoprecipitation and bimolecular fluorescence complementation revealed that ITGB2, but not ITGB1, directly interacts with Rac1 during osteoclast differentiation. Activated Rac1 promotes osteoclast differentiation and bone resorption through several mechanisms. ITGB2 knockdown reduced Rac1-GTP levels and increased ITGB1 expression. ITGB2 inhibition reduced actin ring formation and microtubule migration to the cell edge during osteoclast differentiation. Additionally, overexpression of ITGB1 in ITGB2-knockdown cells not only further suppressed ITGB2 expression but also exacerbated the inhibition of osteoclast differentiation. In a DMM mouse model, ITGB2 was associated with osteoclast activity in the subchondral bone. ITGB2 knockdown significantly reduced bone resorption and slowed OA progression by inhibiting osteoclastogenesis. In conclusion, our study identified a novel mechanism for the reciprocal regulation of integrin subunits. Moreover, inhibition of the ITGB2 signalling pathway slows subchondral bone remodelling in osteoarthritis by inhibiting osteoclast differentiation, offering a potential strategy for targeted therapeutic interventions.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70107"},"PeriodicalIF":5.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolutionary Analysis of Transcriptional Regulation Mediated by Cdx2 in Rodents.","authors":"Weizheng Liang, Guipeng Li, Yukai Wang, Wencheng Wei, Rui Chen, Siyue Sun, Diwen Gan, Hongyang Yi, Bernhard Schaefke, Yuhui Hu, Qi Zhou, Wei Li, Huanhuan Cui, Wei Chen","doi":"10.1111/cpr.70103","DOIUrl":"https://doi.org/10.1111/cpr.70103","url":null,"abstract":"<p><p>Differences in gene expression, which arise from divergence in cis-regulatory elements or alterations in transcription factors (TFs) binding specificity, are one of the most important causes of phenotypic diversity during evolution. On one hand, changes in the cis-elements located in the vicinity of target genes affect TF binding and/or local chromatin environment, thereby modulating gene expression in cis. On the other hand, alterations in trans-factors influence the expression of their target genes in a more pleiotropic fashion. Although the evolution of amino acid sequences is much slower than that of non-coding regulatory elements, particularly for the TF DNA binding domains (DBDs), it is still possible that changes in TF-DBD might have the potential to drive large phenotypic changes if the resulting effects have a net positive effect on the organism's fitness. If so, species-specific changes in TF-DBD might be positively selected. So far, however, this possibility has been largely unexplored. By protein sequence analysis, we observed high sequence conservation in the DBD of the TF caudal-type homeobox 2 across many vertebrates, whereas three amino acid changes were exclusively found in mouse Cdx2 (mCdx2), suggesting potential positive selection in the mouse lineage. Multi-omics analyses were then carried out to investigate the effects of these changes. Surprisingly, there were no significant functional differences between mCdx2 and its rat homologue (rCdx2), and none of the three amino acid changes had any impact on its function. Finally, we used rat-mouse allodiploid embryonic stem cells to study the cis effects of Cdx2-mediated gene regulation between the two rodents. Interestingly, whereas Cdx2 binding is largely divergent between mouse and rat, the transcriptional effect induced by Cdx2 is conserved to a much larger extent. There were no significant functional differences between mCdx2 and its rat homologue (rCdx2), and none of the three amino acid changes had any impact on its function. Moreover, Cdx2 binding is largely divergent between mouse and rat; the transcriptional effect induced by Cdx2 is conserved to a much larger extent.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70103"},"PeriodicalIF":5.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MFG-E8 Accelerates Abdominal Aortic Aneurysm Formation by Enhancing ERK MAPK/NOX4 Axis-Associated Oxidative Stress","authors":"Jie Xiao,&nbsp;Hai Hu,&nbsp;Minghui Zou,&nbsp;Chenhao Li,&nbsp;Dawei Deng,&nbsp;Xing Chen,&nbsp;Jinping Liu","doi":"10.1111/cpr.70104","DOIUrl":"10.1111/cpr.70104","url":null,"abstract":"<p>MFG-E8 promotes oxidative stress by upregulating NOX4 and activating the MAPK pathway, which increases ROS production and affects vascular smooth muscle cell (VSMC) apoptosis, thereby driving the progression of abdominal aortic aneurysm (AAA). Resveratrol can inhibit the expression and function of MFG-E8, reduce ROS generation, and lower the incidence and severity of AAA, making it a potential therapeutic agent for AAA. \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"58 10","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.70104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding the Plasticity of Cancer-Associated Fibroblasts: Mechanistic Insights and Precision Targeting Strategies in Gastric Cancer Progression and Therapeutic Resistance","authors":"Shiyang Deng,&nbsp;Yong zhen Chen,&nbsp;Jiang Du","doi":"10.1111/cpr.70094","DOIUrl":"10.1111/cpr.70094","url":null,"abstract":"&lt;p&gt;Gastric cancer (GC), the fourth leading cause of global cancer mortality, remains clinically problematic despite advances in multimodal treatments including surgery, chemotherapy, and immunotherapy. The consistently poor outcome in advanced stages needs new treatment approaches. Cancer-associated fibroblasts (CAFs) have emerged as important regulators of gastric tumour growth by dynamic interactions inside the tumour microenvironment (TME). These heterogeneous stromal elements, which are produced from several precursors, show continuous phenotypic evolution during carcinogenesis. CAFs mediate tumour-stroma crosstalk by extracellular matrix remodelling, paracrine signalling via growth factors/cytokines, and extracellular vesicle communication. Notably, CAFs and malignant cells show therapeutic pressure-driven co-evolution, and CAF-derived IL-6/IL-8 activate STAT3/NF-κB pathways to promote metabolic reprogramming while also creating drug-resistant ECM barriers. We aim to provide a transformative framework for understanding CAFs biology in gastric oncology, analysing molecular mechanisms of invasion, explaining tumour-CAF co-evolution dynamics, and mapping resistance-related regulatory networks.&lt;/p&gt;&lt;p&gt;Cancer-associated fibroblasts (CAFs) originate from diverse cellular precursors within the tumour microenvironment, including activated fibroblasts, endothelial cells, epithelial cells undergoing epithelial-mesenchymal transition (EMT), mesenchymal/haematopoietic stem cells [&lt;span&gt;1&lt;/span&gt;], adipocytes, pericytes, and stellate cells. Their transformation is governed by growth factors (e.g., TGF-β, PDGF, FGF, HGF), inflammatory cytokines (e.g., TNF, IL-6), and genetic alterations such as RAS/Myc oncogenic mutations or p53/PTEN tumour suppressor inactivation. CAFs heterogeneity stems from their multipotent origins, reflected in divergent surface markers and functional profiles. Single-cell analyses have resolved six functionally distinct CAF subclasses: three dominant subtypes—myofibroblastic (CAF-myo), inflammatory (CAF-infla), and adipose-derived (CAF-adi)—and three minor subsets including endothelial-mesenchymal transition (CAF-EndMT), peripheral nerve-like (CAF-PN), and antigen-presenting (CAF-ap) variants. Functionally, CAF subpopulations differentially regulate tumour progression through cancer cell proliferation, angiogenesis, ECM remodelling, and immunosuppression [&lt;span&gt;2&lt;/span&gt;] (Table 1).&lt;/p&gt;&lt;p&gt;The extracellular matrix (ECM) is a complex network structure maintained in a dynamic equilibrium, primarily composed of proteins, polysaccharides, and hydrated gels. CAFs contribute to the remodelling of the tumour microenvironment at multiple levels, including the regulation of ECM stiffness, synthesis of matrix proteins, and degradation of ECM components, through the secretion of various biologically active molecules, thereby promoting the invasive process of tumour cells. Research has shown that CAFs upregulate the expression of HAPLN1 through th","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"58 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.70094","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FAM20A Deficiency Drives Transcriptomic Dysregulation and Functional Impairment in Gingival Fibroblasts.","authors":"Kanokwan Sriwattanapong, Sermporn Thaweesapphithak, Chompak Khamwachirapitak, Pannagorn Sae-Ear, Sasiprapa Prommanee, Noppadol Sa-Ard-Iam, Suphalak Phothichailert, Han Sung Jung, Vorasuk Shotelersuk, Thantrira Porntaveetus","doi":"10.1111/cpr.70096","DOIUrl":"https://doi.org/10.1111/cpr.70096","url":null,"abstract":"<p><p>Amelogenesis imperfecta type 1G (AI1G), also known as Enamel-Renal-Gingival Syndrome (ERGS), is an autosomal recessive disorder caused by variants in FAM20A, encoding a Golgi apparatus protein crucial for protein processing and secretion. AI1G presents with enamel defects, nephrocalcinosis and gingival overgrowth. Building upon our previous findings demonstrating the impact of FAM20A insufficiency on deciduous dental pulp cells, this study investigated the molecular mechanisms underlying gingival fibromatosis in AI1G. RNA sequencing of gingival fibroblasts from an AI1G patient revealed widespread differential gene expression (DEG). Gene Ontology (GO) analysis demonstrated enrichment of DEGs in biological processes related to cell adhesion, differentiation, proliferation (including positive regulation and cell division), cell cycle regulation, apoptosis and signal transduction. Pathway analysis (Reactome and KEGG) further highlighted the dysregulation of signalling pathways, including Wnt, TGF-β, cell cycle, DNA replication, Rho GTPase signalling and extracellular matrix organisation. Functional assays confirmed these findings, revealing delayed initial attachment and spreading, impaired osteogenic differentiation (evidenced by reduced mineralization and downregulation of DLX5, OCN, RUNX2 and OPN), enhanced cell cycle progression and proliferation (increased colony size and proliferation rates, along with a shift from G0/G1 to G2/M phase) and suppressed apoptosis in FAM20A-insufficient fibroblasts. These results suggest that FAM20A plays a critical role in regulating fundamental processes in gingival fibroblasts, and its insufficiency contributes to the gingival fibromatosis phenotype observed in AI1G through the disruption of cell adhesion, differentiation, proliferation and apoptosis. This study proposes novel insights into the pathogenesis of AI1G and highlights potential therapeutic targets for this complex disorder.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70096"},"PeriodicalIF":5.9,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Comparison of Seven CD19 CAR Designs in Engineering NK Cells for Enhancing Anti-Tumour Activity”","authors":"","doi":"10.1111/cpr.70098","DOIUrl":"10.1111/cpr.70098","url":null,"abstract":"<p>Y. Wang, J. H. Li, Z. Q. Wang, J. Li, Z. Wang, Y. Liu, T. Wang, M. Zhang, C. Xia, F. Zhang, D. Huang, L. Zhang, Y. Zhao, L. Liu, Y. Zhu, H. Qi, X. Zhu, W. Qian, F. Hu and J. Wang, “Comparison of Seven CD19 CAR Designs in Engineering NK Cells for Enhancing Anti-Tumour Activity,” <i>Cell Proliferation</i> 57, no. 11 (2024): e13683. https://doi.org/10.1111/cpr.13683.</p><p>In Figure 1A, the promoters of the SFG vector in structure schematic diagrams were mistakenly labelled as “α-globin”. The errors do not affect the rest of the article. The incorrect version is shown below:</p><p>The corrected Figure 1 and accompanying legend appear below.</p><p>The incorrect Figure:</p><p>Corrected Figure:</p><p>We apologize for the errors.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"58 10","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.70098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR Technology in Disease Management: An Updated Review of Clinical Translation and Therapeutic Potential.","authors":"Bahareh Farasati Far, Marziyeh Akbari, Mohammad Amin Habibi, Morteza Katavand, Sherko Nasseri","doi":"10.1111/cpr.70099","DOIUrl":"https://doi.org/10.1111/cpr.70099","url":null,"abstract":"<p><p>CRISPR-Cas9 technology has rapidly advanced as a transformative genome-editing platform, facilitating precise genetic modifications and expanding therapeutic opportunities across various diseases. This review explores recent developments and clinical translations of CRISPR applications in oncology, genetic and neurological disorders, infectious diseases, immunotherapy, diagnostics, and epigenome editing. CRISPR has notably progressed in oncology, where it enables the identification of novel cancer drivers, elucidation of resistance mechanisms, and improvement of immunotherapies through engineered T cells, including PD-1 knockout CAR-T cells. Clinical trials employing CRISPR-edited cells are demonstrating promising results in hematologic malignancies and solid tumours. In genetic disorders, such as hemoglobinopathies and muscular dystrophies, CRISPR-Cas9 alongside advanced editors like base and prime editors show significant potential for correcting pathogenic mutations. This potential was affirmed with the FDA's first approval of a CRISPR-based therapy, Casgevy, for sickle cell disease in 2023. Neurological disorders, including Alzheimer's, ALS, and Huntington's disease, are increasingly targeted by CRISPR approaches for disease modelling and potential therapeutic intervention. In infectious diseases, CRISPR-based diagnostics such as SHERLOCK and DETECTR provide rapid, sensitive nucleic acid detection, particularly valuable in pathogen outbreaks like SARS-CoV-2. Therapeutically, CRISPR systems target viral and bacterial genomes, offering novel treatment modalities. Additionally, CRISPR-mediated epigenome editing enables precise regulation of gene expression, expanding therapeutic possibilities. Despite these advances, significant challenges remain, including off-target effects, delivery methodologies, immune responses, and long-term genomic safety concerns. Future improvements in editor precision, innovative delivery platforms, and enhanced safety assessments will be essential to fully integrate CRISPR-based interventions into standard clinical practice, significantly advancing personalised medicine.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70099"},"PeriodicalIF":5.9,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reversal of MPPa-PDT Resistance in Osteosarcoma by Targeting ROCK2-Mediated Autophagy.","authors":"Xuan Yi, Xueqiang Deng, Jianyong Deng, Chen Li, Hong Peng, Yunyan Du, Qing Li, Xiaohua Yan, Xin Hu, Yan Zheng, Shenliang Chen, Ting Xiong, Debin Xu, Leifeng Chen, Liang Hao","doi":"10.1111/cpr.70097","DOIUrl":"https://doi.org/10.1111/cpr.70097","url":null,"abstract":"<p><p>Osteosarcoma (OS) is a primary bone tumour that occurs mostly in adolescents and is associated with a high degree of malignancy, early metastasis, and poor prognosis. Pyropheophorbide-a methyl ester-Photodynamic therapy (MPPa-PDT) is a new approach for the clinical treatment of osteosarcoma that develops after surgery and radiotherapy; however, the presence of MPPa-PDT resistance in osteosarcoma greatly limits its efficacy. In this study, we found that Rho-associated coiled-coil containing protein kinase 2 (ROCK2) expression increased in osteosarcoma cells after MPPa-PDT treatment. ROCK2 inhibition results in osteosarcoma sensitivity to MPPa-PDT and is accompanied by a decrease in cellular autophagy levels. Rescue experiments further showed that ROCK2 mediates MPPa-PDT resistance in osteosarcoma by regulating autophagy. Mechanistic studies have shown that ROCK2 mediates autophagy in osteosarcoma cells by regulating the Hippo signalling pathway. ROCK2 overexpression resulted in increased levels of the ROCK2-Salvador homology 1 (SAV1) complex and decreased levels of the mammalian STE20-like protein kinase 1 (MST1)-SAV1 complex, thereby inhibiting activation of the Hippo pathway, which in turn led to osteosarcoma MPPa-PDT resistance by regulating cellular autophagy. ROCK2 competes with MST1 for binding to the aa 28-198 region of SAV1. We also confirmed from a clinical perspective that ROCK2 is an independent prognostic factor in patients with osteosarcoma, is associated with worse patient prognosis, and correlates with the Hippo pathway. Targeted inhibition of ROCK2 by screening for J059-0149 increases the sensitivity of osteosarcoma to MPPa-PDT. In conclusion, our study establishes a novel mechanism to reverse MPPa-PDT resistance in osteosarcoma by targeting ROCK2-mediated autophagy, providing new targets and research ideas for the clinical treatment of osteosarcoma MPPa-PDT resistance.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70097"},"PeriodicalIF":5.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocrine Resistance Score Based on Three Key Genes Predicts Prognosis and Reveals Potential Therapeutic Targets for ER+HER2- Breast Cancer.","authors":"Liqin Ping, Lewei Zhu, Nian Chen, Xikun Liu, Jirui Zhong, Xiaoqing Sun, Hailin Tang, Kaiming Zhang","doi":"10.1111/cpr.70100","DOIUrl":"https://doi.org/10.1111/cpr.70100","url":null,"abstract":"<p><p>Endocrine resistance is a leading cause of mortality in oestrogen receptor-positive and human epidermal growth factor receptor 2-negative (ER+HER2-) breast cancer (BC), highlighting the urgent need to understand its underlying molecular mechanisms and identify potentially resistant patients for effective management. In this study, we constructed endocrine-resistant cell lines through long-term oestrogen deprivation and identified differentially expressed genes (DEGs) via transcriptome analysis. Key endocrine-resistant genes were defined through Cox regression analysis. Our findings revealed that the genes CLEC3A, PCDH10, and ST3GAL1 were significantly upregulated in endocrine-resistant cells and serve as independent prognostic factors for ER+HER2- BC patients. We developed an endocrine resistance score (ERS), and a nomogram model incorporating ERS demonstrated robust predictive capabilities for patient prognosis. Single-cell RNA sequencing analysis demonstrated that the ERS and the three core genes constituting the ERS were significantly upregulated in tissue specimens from patients with resistance to endocrine neoadjuvant therapy. Additionally, knocking down CLEC3A, PCDH10, and ST3GAL1 led to reduced malignancy progression in endocrine-resistant BC cells. Mechanistic studies revealed that CLEC3A promotes endocrine resistance by upregulating the PI3K-AKT pathway. This study suggests that CLEC3A, PCDH10, and ST3GAL1 are associated with endocrine resistance and can reflect the prognosis of ER+HER2- BC patients receiving endocrine therapy, providing potential therapeutic targets and a valuable prognostic indicator for clinicians.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70100"},"PeriodicalIF":5.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment and Validation of a C57BL/6J Mouse Model for Melasma.","authors":"Wenzhu Wang, Xiaojie Sun, Yunyao Liu, Yin Yang, Hedan Yang, Xiaoli Zhang, Xiuzhen Li, Haoxiang Xu, Xu Chen, Tong Lin","doi":"10.1111/cpr.70078","DOIUrl":"https://doi.org/10.1111/cpr.70078","url":null,"abstract":"<p><p>Melasma is a recurrent and treatment-resistant hyperpigmentation disorder characterized by a complex and multifactorial pathogenesis. However, the lack of a stable and reliable animal model has hindered systematic investigations into its onset and progression. In this study, we established a melasma-like model in C57BL/6J mice by combining broadband UVB irradiation, intramuscular progesterone administration, and induced emotional stress. The affected skin areas exhibited irregular, brown hyperpigmented patches. Histopathological analysis revealed an accumulation of melanin granules in the epidermis and superficial dermis, elevated levels of tyrosinase (TYR) in both skin and plasma, systemic oxidative stress imbalance, and reduced autophagic activity in the lesional skin. Furthermore, this model displayed distinct differences from a UV-induced post-inflammatory hyperpigmentation (PIH) model. Notably, the melasma-like mice responded to tranexamic acid treatment in a manner that closely resembled clinical outcomes observed in human patients. Collectively, these findings establish a stable, reproducible, and clinically relevant mouse model of melasma, providing a valuable platform for future research into its pathogenesis and treatment.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70078"},"PeriodicalIF":5.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}