Pathology, research and practice最新文献

{"title":"Long-term effects of fenofibrate in male offspring of gestational diabetic rats: Evaluation of glycemia, lipid profiles, liver tissue, and metabolic alterations","authors":"Shan Wang ,&nbsp;Lin Qin ,&nbsp;Xiaoli Song ,&nbsp;Hejia Yin ,&nbsp;Weihong Yang ,&nbsp;Robabe Bazesh","doi":"10.1016/j.prp.2025.156331","DOIUrl":"10.1016/j.prp.2025.156331","url":null,"abstract":"<div><h3>Introduction</h3><div>Fenofibrate (FenoF) has demonstrated potential in regulating glycemia and lipid profiles across various metabolic disorders. However, its effects on the offspring of rats with gestational diabetes mellitus (GDM) have not yet been investigated. This study aims to evaluate the long-term effects of FenoF on glycemic control, lipid metabolism, liver histology, and the expression of key metabolic and inflammatory proteins in the offspring of GDM-exposed rats.</div></div><div><h3>Materials and methods</h3><div>Pregnant Wistar rats were randomly assigned to four groups (n = 4 per group): Control, GDM, FenoF-treated (100 mg/kg/day, orally), and GDM rats treated with FenoF (GDM + FenoF). Diabetes was induced via a single intraperitoneal injection of streptozotocin (50 mg/kg) on gestational day 12. Six male offspring from each group were randomly selected and maintained on a standard chow diet. The offspring were reared until adulthood (12 weeks of age), at which point plasma glucose levels, lipid profiles, and liver tissue alterations were evaluated through histopathological analysis and Western blotting.</div></div><div><h3>Results</h3><div>FenoF treatment significantly reduced triglyceride, low-density lipoprotein cholesterol (LDL-C), and glucose levels (P &lt; 0.05), while significantly increasing high-density lipoprotein cholesterol (HDL-C) levels (P &lt; 0.05) in the offspring of GDM rats. FenoF exerted an ameliorative effect in GDM rat offspring, as evidenced by a significant reduction in hepatic TNF-α expression (P &lt; 0.001) and a marked increase in PPARα levels (P &lt; 0.001) compared to the untreated GDM group. Western blot analysis revealed that FenoF treatment significantly downregulated TLR4 and NF-κB expression, indicating attenuation of inflammatory signaling. Moreover, FenoF treatment significantly upregulated AKT1, IRS1, and CPT1A levels, suggesting enhanced insulin signaling and lipid metabolism. Additionally, Histopathological analysis demonstrated that FenoF preserved liver architecture and significantly reduced inflammation and structural abnormalities relative to GDM controls.</div></div><div><h3>Conclusion</h3><div>In the context of gestational diabetes, FenoF appears to be a promising therapeutic candidate for improving glucose and lipid homeostasis, protecting hepatic tissue from diabetes-induced damage and inflammation, and enhancing key metabolic pathways in the offspring of GDM rats.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156331"},"PeriodicalIF":3.2,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145775393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microdissection: Insights and progress in the era of precision medicine","authors":"Maxime Golias ,&nbsp;Zuzana Krupova ,&nbsp;Pierre Defrenaix ,&nbsp;Marie-Françoise Heymann ,&nbsp;Dominique Heymann","doi":"10.1016/j.prp.2025.156328","DOIUrl":"10.1016/j.prp.2025.156328","url":null,"abstract":"<div><div>Intratumoral heterogeneity is a real challenge for understanding the key mechanisms involved in cancer progression, but also for pathologists to make a reliable diagnosis. The development of precision medicine in oncology allows each treatment to be tailored to the specific characteristics of the tumours. However, the ability to isolate pure cell populations is a very difficult task and makes accurate analysis difficult. The development since the 90’s of precise dissection techniques, known as microdissection, has helped to overcome problems associated with tumor heterogeneity. Since then, a few techniques have been developed that provide dissection accuracy down to the sub-cellular level. These technologies have enabled key principles to be understood in basic research but handling difficulties have prevented their use in pathology laboratories. Working with microquantities can also be a difficult task and requires several technical adaptations. This review provides an overview of all microdissection techniques currently available. In addition to their main advantages, examples of applications and adaptations of molecular biology techniques to microquantities are proposed to illustrate the interest of these technical approaches in both basic research and clinical applications.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156328"},"PeriodicalIF":3.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nodal T-follicular helper cell lymphoma with hodgkin/reed-sternberg-like cells: Clinicopathologic and molecular characterization of 11 cases","authors":"Linlin Huang ,&nbsp;Jing Li ,&nbsp;Huawen Wang ,&nbsp;Mei Tang ,&nbsp;Min Jing ,&nbsp;Xinyi Shi ,&nbsp;Yongkun Xiao ,&nbsp;Lu Bai ,&nbsp;Ling Wang ,&nbsp;Dong Liu ,&nbsp;Tao Wu ,&nbsp;Chao Ding ,&nbsp;Jinglong Lv ,&nbsp;Huami Ye ,&nbsp;Jing Li ,&nbsp;Jiamei Fan ,&nbsp;Pengchun Wu ,&nbsp;Wenbo Zhou ,&nbsp;Xiaohui Wu ,&nbsp;Hongwei Wang","doi":"10.1016/j.prp.2025.156327","DOIUrl":"10.1016/j.prp.2025.156327","url":null,"abstract":"<div><h3>Background</h3><div>Angioimmunoblastic T-cell lymphoma (AITL), a subtype of nodal T-follicullar helper (TFH) cell lymphoma, may pccasionally contain Hodgkin/Reed-Sternberg (HRS)-like cells, which poses significant diagnostic challenges. These large atypical cells ofthen express CD30 and weak PAX5, making classical Hodgkin lymphoma (CHL) and increasing the risk of misdiagnosis. Accurate recognition requires integration of histological, immunophenotypic, viral, and molecular features.</div></div><div><h3>Method</h3><div>We retrospectively analyzed 11 patients diagnosed with AITL containing HRS-like cells between January 2020 and January 2025. All cases were consultation cases from a regional lymphoma diagnostic center, with available formalin-fixed, paraffin-embedded lymph node tissue. A comprehensive review included histomorphology, immunohistochemistry, Epstein-Barr virus-encoded RNA (EBER) in situ hybridization, T-cell receptor (TCR) and immunoglobulin (IG) gene rearrangement studies, and targeted next-generation sequencing (NGS) of lymphoma-associated genes.</div></div><div><h3>Results</h3><div>The cohort included 7 men and 4 women, with a median age of 63 years. Histologically, all cases showed partial to complete effacement of nodal architecture, proliferation of high endothelial venules, expansion of follicular dendritic cell (FDC) meshworks, and scattered HRS-like cells. Immunophenotypically, HRS-like cells were consistently CD30-positive, weak PAX5-positive (9/11), and variably CD15-positive. Background T cells expressed TFH markers including CD4, PD-1, CD10, BCL-6, CXCL13, and ICOS. EBER was positive in 10 cases. TCR gene clonality was detected in 9 patients, while 2 also showed B-cell clonality. NGS identified frequent mutations in <em>TET2</em> (11/11) and <em>RHOA</em> (8/11), with additional alterations in <em>DNMT3A, KMT2D, CREBBP, BRD4</em>, and <em>PLCG1</em>.</div></div><div><h3>Conclusions</h3><div>AITL with HRS-like cells is prone to misdiagnosis as CHL due to overlapping morphological and immunophenotypic features. Integration of EBER, TCR/IG clonality assessment, and molecular profiling, particularly the identification of <em>TET2</em> and <em>RHOA</em> mutations is essential for accurate classification. Recognizing this entity is critical for avoiding diagnostic pitfalls and guiding appropriate therapeutic strategies.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156327"},"PeriodicalIF":3.2,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing glioblastoma immunotherapy: Molecular pathways and innovative therapeutic strategies","authors":"Min Tang ,&nbsp;Pengpeng Xu ,&nbsp;Xiaogang Zhang","doi":"10.1016/j.prp.2025.156326","DOIUrl":"10.1016/j.prp.2025.156326","url":null,"abstract":"<div><div>Glioblastoma (GBM) has been an aggressive brain tumor and it demonstrates poor prognosis and resistance to the traditional therapeutics. GBM is characterized by abnormal proliferation, high growth, and a significantly immunosuppressive tumor microenvironment (TME), making immunotherapy as an ideal treatment for GBM. The recent advances in the field of immunotherapy such as vaccines, and CAR-T cell treatments, have demonstrated significant efficacy in accelerating anticancer immune responses and improving survival outcomes. Immune checkpoint drugs targeting CTLA-4 and PD-1/PD-L1 have demonstrated synergistic effects in enhancing T cell activation and infiltration. Vaccines such as DCVax-L and oncolytic viruses including G47Δ have demonstrated promising outcomes in the clinical studies. CAR-T cell treatments have been directed against particular antigens such as EGFRvIII and IL13Rα2 and have demonstrated considerable antitumor efficacy. Nonetheless, there are a number of challenges to be considered including the immunosuppressive TME, the blood-brain barrier (BBB), and the molecular heterogeneity of GBM. Addressing these challenges requires a versatile strategy, encompassing the development of innovative combination drugs, complicated imaging methodologies to evaluate treatment efficacy, and the discovery of biomarkers to predict patient responses to immunotherapy. The future research can focus on highlighting the complicated connections between the immune system and GBM, utilizing perspectives from preclinical models and clinical studies to formulate more effective and customized treatment options. This review emphasizes on the recent research results and clinical data, providing insights into prospective developments in GBM immunotherapy and highlighting the necessity of a comprehensive strategy to enhance patient outcomes.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156326"},"PeriodicalIF":3.2,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute myeloid leukemia with plasmacytoid dendritic cell differentiation initially presenting as skin lesions: A case report","authors":"Chenxi Xiang ,&nbsp;Shaoqi Li ,&nbsp;Jia Liu ,&nbsp;Qianqian Yin ,&nbsp;Dongshen Ma ,&nbsp;Hui Liu","doi":"10.1016/j.prp.2025.156324","DOIUrl":"10.1016/j.prp.2025.156324","url":null,"abstract":"<div><div>Plasmacytoid dendritic cell (pDC) accumulations are frequently observed in association with myeloid neoplasms in the bone marrow. We report a case diagnosed as acute myeloid leukemia (AML) with pDC differentiation, which first presented as skin lesions and lymphadenopathies. The skin biopsy revealed pDC-like cells infiltrating the dermal layer. The architecture of the cervical lymph node remained largely preserved, but it was infiltrated by monotonous, atypical cells with a pDC-like immunophenotype in the interfollicular areas. Flow cytometry analysis of the lymph node tissue confirmed the heterogeneity and pDC-like immunophenotype of the tumor cells. Furthermore, a bone marrow biopsy confirmed the presence of underlying AML. DNA sequencing demonstrated that the tumor cells in both the tumor cells in the lymph node and skin biopsy shared the identical genetic abberations as in the bone marrow. Based on these findings, a diagnosis of AML with pDC differentiation was established.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156324"},"PeriodicalIF":3.2,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145725153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a lactylation-related molecular classification and machine learning-based gene signature to predict survival, response to immunotherapy for ovarian cancer","authors":"Nannan Luan ,&nbsp;Feng Jin ,&nbsp;Zhenhua Hu ,&nbsp;Miao Lu ,&nbsp;Jian Gao ,&nbsp;Liancheng Zhu","doi":"10.1016/j.prp.2025.156325","DOIUrl":"10.1016/j.prp.2025.156325","url":null,"abstract":"<div><h3>Background</h3><div>Lactylation is acknowledged as a regulator of numerous biological processes related to cancer. Research on the ability of lactylation-related genes (LacRGs) to predict prognosis and immunotherapeutic response in ovarian cancer (OC) patients is limited.</div></div><div><h3>Methods</h3><div>Consensus clustering was utilized to identify prognostic differentially expressed genes (DEGs) across clusters. A consensus lactylation-related gene signature (LRGS) was established from TCGA-OC and four independent GSE datasets through a machine learning-based integrative approach.</div></div><div><h3>Results</h3><div>LRGS demonstrates consistent and robust performance as an independent risk factor for overall survival. Furthermore, while the low-LRGS group is more likely to exhibit the \"hot tumor\" phenotype, it also shows a more favorable prognosis and enhanced responsiveness to immunotherapy. Patients exhibiting a high LRGS demonstrated a reduced probability of deriving benefit from immunotherapy and faced a poor prognosis. The oncogenic role of the risk gene RPS6KA2 was preliminarily validated.</div></div><div><h3>Conclusions</h3><div>An in-depth analysis of the LacRGs data may yield valuable insights and enhance the molecular classification of OC. The identification of LRGS serves as a crucial factor in the early prognosis of patients and the selection of potential candidates for immunotherapy. The findings have significant implications for individual patients with OC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156325"},"PeriodicalIF":3.2,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145725127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA-based mechanisms underlying oncogenicity and drug resistance in NRG1-rearranged non-small cell lung cancer","authors":"Ameeduzzafar Zafar ,&nbsp;Omar Awad Alsaidan ,&nbsp;Mohammad Khalid ,&nbsp;Md Ali Mujtaba ,&nbsp;Ali Alquraini ,&nbsp;Mohd Yasir","doi":"10.1016/j.prp.2025.156323","DOIUrl":"10.1016/j.prp.2025.156323","url":null,"abstract":"<div><div>Non-small cell lung cancer (NSCLC), accounting for nearly 85 % of lung tumors, remains one of the most fatal cancers worldwide. Among the various oncogenic drivers identified in NSCLC, neuregulin-1 (NRG1) gene fusions, though rare, occurring in approximately 0.1–0.3 % of cases, are clinically significant, particularly in invasive mucinous adenocarcinomas. These genomic events trigger abnormal heterodimerization of ERBB2 and ERBB3, stimulating downstream PI3K/AKT and MAPK pathways, which in turn foster uncontrolled growth, metastatic potential, and therapeutic resistance. These genomic events cause ERBB2 and ERBB3 to form abnormal heterodimers that activate downstream PI3K/AKT and MAPK signaling pathways, driving uncontrolled growth, metastasis, and therapeutic resistance. Alongside these mechanisms, non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have emerged as pivotal regulators of cancer-related networks. Although they do not encode proteins, ncRNAs exert influence at transcriptional, post-transcriptional, and epigenetic levels, with the capacity to either suppress or enhance oncogenic processes. This review examines the interplay between ncRNA activity and NRG1 fusion-driven signaling in NSCLC, highlighting their roles in modulating pathways and contributing to drug resistance. Tumor-suppressive miRNAs, such as miR-22 and miR-296–5p, directly target NRG1 or ERBB2/ERBB3 transcripts, thereby weakening aberrant signaling cascades. Conversely, oncogenic ncRNAs like MALAT1 and HOTAIR facilitate epithelial–mesenchymal transition, cell proliferation, and chemoresistance, while circRNAs amplify oncogenic effects by acting as miRNA sponges. Collectively, these regulatory molecules shape the oncogenic landscape of NRG1-rearranged NSCLC and influence therapeutic outcomes. Dysregulated ncRNAs thus hold promise as biomarkers for diagnosis, prognosis, and treatment planning, with therapeutic strategies aimed at restoring tumor-suppressive ncRNAs or inhibiting oncogenic ones offering a potential avenue to overcome resistance in this subset of patients.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156323"},"PeriodicalIF":3.2,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathological features and diagnostic challenges of early gastric cardiac carcinoma with dysplastic gastritis cystica profunda: A case report","authors":"Wanlun Wang ,&nbsp;Si Wu ,&nbsp;Jie Luo ,&nbsp;Jiale Ji ,&nbsp;Jianhua Dai ,&nbsp;Senlin Xu","doi":"10.1016/j.prp.2025.156313","DOIUrl":"10.1016/j.prp.2025.156313","url":null,"abstract":"<div><div>Gastric cardiac carcinoma associated with dysplastic gastritis cystica profunda (GCP) with represents a rare clinicopathological entity. Its distinct histological features pose diagnostic challenges, as GCP with mild dysplasia can mimic invasive carcinoma, potentially leading to overdiagnosis, overtreatment, and increased patient morbidity. We report a case of early gastric cardiac carcinoma with dysplastic GCP, treated by endoscopic submucosal dissection (ESD). Histopathological examination revealed a moderately differentiated tubular adenocarcinoma confined to the mucosa, adjacent to submucosal cystic glands exhibiting mild dysplasia, cystic dilation, abundant mucin secretion, and focal mucin pools. Immunohistochemically, the carcinoma was positive for CK7 but negative for MUC2 and MUC5AC, while the cystic glands showed the opposite profile. The Ki67 proliferative index was significantly lower in the cystic glands than in the carcinoma. The final diagnosis was intramucosal moderately differentiated adenocarcinoma of the gastric cardia with mildly dysplastic GCP. No recurrence was observed during the 12-month follow-up. This case highlights the diagnostic pitfalls of this entity, and underscores the importance of accurate pathological recognition to guide clinical management.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156313"},"PeriodicalIF":3.2,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipokine-mediated crosstalk between metabolic dysregulation and inflammatory pathways","authors":"Zhiheng He ,&nbsp;Linjie Zhao ,&nbsp;Jiarui Liu ,&nbsp;Wanjie Zheng ,&nbsp;Chengjun Gong ,&nbsp;Chengxuan Gong ,&nbsp;Li Guo ,&nbsp;Tingming Liang","doi":"10.1016/j.prp.2025.156312","DOIUrl":"10.1016/j.prp.2025.156312","url":null,"abstract":"<div><div>Adipokines are bioactive signaling molecules secreted by adipose tissue that play crucial roles in the regulation of energy metabolism and inflammatory responses. With the global rise in obesity and related metabolic disorders, understanding adipokine-mediated regulation has become increasingly important for addressing chronic inflammation and its systemic consequences. However, the adipokine-mediated crosstalk between metabolic dysregulation and inflammatory pathways remains incompletely understood. Beyond classical adipokines, adipose tissue-derived microRNAs (miRNAs) have been identified as novel paracrine and endocrine signaling molecules, capable of modulating distant cellular functions through exosome-mediated transport. These extracellular vesicle-encapsulated miRNAs are increasingly recognized as key regulators in inter-organ communication and disease development. This review summarizes the current understanding of adipokine secretion mechanisms, roles in metabolic and inflammatory regulation, and the dual functions in both metabolic diseases and cancer. Emerging therapeutic strategies focusing on targeting adipokines and the signaling pathways downstream are also discussed, highlighting the translational potential of adipokines as promising biomarkers and therapeutic targets for the prevention and treatment of metabolic diseases and cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156312"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145652025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ACLP promotes hypertrophic scar pathogenesis by enhancing myofibroblast activation and cholesterol synthesis-related gene expression","authors":"Yi Shi,&nbsp;Yajuan Song,&nbsp;Tong Wang,&nbsp;Yan Jiao,&nbsp;Juanli Dang,&nbsp;Yufei Zhang,&nbsp;Shu’ao Xiao,&nbsp;Baoqiang Song,&nbsp;Zhou Yu","doi":"10.1016/j.prp.2025.156311","DOIUrl":"10.1016/j.prp.2025.156311","url":null,"abstract":"<div><h3>Background</h3><div>Hypertrophic scar (HS) is a severe fibrotic disease characterized by excessive fibroblast activation and extracellular matrix deposition. While previous studies have revealed the involvement of Aortic Carboxypeptidase Like Protein (ACLP) in other fibrotic diseases, the role of ACLP in HS has not been investigated.</div></div><div><h3>Methods</h3><div>Quantitative real-time PCR (qRT-PCR), Western blotting, and immunofluorescence were applied to investigate the expression and subcellular location of ACLP. Wound healing and Transwell assays were employed to evaluate the impact of ACLP on HSF migration after ACLP siRNA transfection or recombinant human ACLP protein (rACLP) stimulation. The protein expression levels of VIM, MMP2, MMP9, α-SMA, COL I, and COL III in HSFs were also analyzed. A collagen gel contraction assay was harnessed to assess the contractile ability of HSFs after ACLP siRNA transfection or rACLP treatment. Lastly, RNA-Seq was utilized to reveal the gene expression profile of HSFs following ACLP knock-down.</div></div><div><h3>Results</h3><div>ACLP expression was increased in both HS tissues and human hypertrophic scar fibroblasts (HSFs). ACLP knock-down attenuated the horizontal and vertical migration of HSFs, collagen gel contraction activity, fibroblast to myofibroblast transition (FMT), and VIM, MMP2, MMP9, α-SMA, and COL III protein expression. Conversely, rACLP stimulation promoted HSF migration, gel contraction, FMT, and associated protein expression. Additionally, ACLP knock-down downregulated the expression of two cholesterol synthesis-related genes comprising HMGCS1 and HMGCR.</div></div><div><h3>Conclusions</h3><div>Here, for the first time, we reveal that ACLP expression is upregulated during HS and that it promotes HSF migration and myofibroblast activation. Hence, ACLP may serve as a candidate biomarker for HS pathogenesis and as an intervention target for HS prevention and treatment.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"277 ","pages":"Article 156311"},"PeriodicalIF":3.2,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145615959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}