American Journal of Pathology最新文献

{"title":"Celebrating the First 100 Years of Publishing Significant Scientific Discoveries in The American Journal of Pathology","authors":"Mark E. Sobel , Martha B. Furie","doi":"10.1016/j.ajpath.2024.10.011","DOIUrl":"10.1016/j.ajpath.2024.10.011","url":null,"abstract":"","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 1","pages":"Pages 2-4"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell Advances in Investigating and Understanding Chronic Kidney Disease and Diabetic Kidney Disease","authors":"Sagar Bhayana ,&nbsp;Philip A. Schytz ,&nbsp;Emma T. Bisgaard Olesen ,&nbsp;Keng Soh ,&nbsp;Vivek Das","doi":"10.1016/j.ajpath.2024.07.007","DOIUrl":"10.1016/j.ajpath.2024.07.007","url":null,"abstract":"<div><div>Chronic kidney disease (CKD) and its subset diabetic kidney disease are progressive conditions that affect &gt;850 million people worldwide. Diabetes, hypertension, and glomerulonephritis are the most common causes of CKD, which is associated with significant patient morbidity and an increased risk of cardiovascular events, such as heart failure, ultimately leading to premature death. Despite newly approved drugs, increasing evidence shows that patients respond to treatment differently given the complexity of disease heterogeneity and complicated pathophysiology. This review article presents an integrative approach to understanding and addressing CKD through the lens of precision medicine and therapeutics. Advancements in single-cell omics technologies and artificial intelligence can be leveraged to explore the intricate cellular mechanisms underlying CKD and diabetic kidney disease pathogenesis. Dissecting the cellular heterogeneity and identifying rare cell populations using single-cell approaches will facilitate uncovering novel therapeutic targets and biomarkers for personalized treatment strategies. Finally, we discuss the potential of artificial intelligence–driven analyses in predicting disease progression and treatment response, thereby paving the way for tailored interventions.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 1","pages":"Pages 55-68"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell Analysis Provides New Insights into the Roles of Tertiary Lymphoid Structures and Immune Cell Infiltration in Kidney Injury and Chronic Kidney Disease","authors":"Takahisa Yoshikawa ,&nbsp;Motoko Yanagita","doi":"10.1016/j.ajpath.2024.07.008","DOIUrl":"10.1016/j.ajpath.2024.07.008","url":null,"abstract":"<div><div>Chronic kidney disease (CKD) is a global health concern with high morbidity and mortality. Acute kidney injury (AKI) is a pivotal risk factor for the progression of CKD, and the rate of AKI-to-CKD progression increases with aging. Intrarenal inflammation is a fundamental mechanism underlying AKI-to-CKD progression. Tertiary lymphoid structures (TLSs), ectopic lymphoid aggregates formed in nonlymphoid organs, develop in aged injured kidneys, but not in young kidneys, with prolonged inflammation and maladaptive repair, which potentially exacerbates AKI-to-CKD progression in aged individuals. Dysregulated immune responses are involved in the pathogenesis of various kidney diseases, such as IgA nephropathy, lupus nephritis, and diabetic kidney diseases, thereby deteriorating kidney function. TLSs also develop in several kidney diseases, including transplanted kidneys and renal cell carcinoma. However, the precise immunologic mechanisms driving AKI-to-CKD progression and development of these kidney diseases remain unclear, which hinders the development of novel therapeutic approaches. This review aims to describe recent findings from single-cell analysis of cellular heterogeneity and complex interactions among immune and renal parenchymal cells, which potentially contribute to the pathogenesis of AKI-to-CKD progression and other kidney diseases, highlighting the mechanisms of formation and pathogenic roles of TLSs in aged injured kidneys.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 1","pages":"Pages 40-54"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Both Classical and Non-Classical Monocytes Patrol Glomerular Capillaries and Promote Acute Glomerular Inflammation","authors":"ZheHao Tan ,&nbsp;Pam Hall ,&nbsp;Matthias Mack ,&nbsp;Sarah L. Snelgrove ,&nbsp;A. Richard Kitching ,&nbsp;Michael J. Hickey","doi":"10.1016/j.ajpath.2024.07.010","DOIUrl":"10.1016/j.ajpath.2024.07.010","url":null,"abstract":"<div><div>Monocyte patrolling of the vasculature has been ascribed primarily to the non-classical monocyte subset. However, a recent study of the glomerular microvasculature provided evidence that both classical and non-classical monocytes undergo periods of intravascular retention and migration. Despite this, whether these subsets contribute differentially to acute glomerular inflammation is unknown. This study used glomerular multiphoton intravital microscopy to investigate the capacity of classical and non-classical monocytes to patrol the glomerular microvasculature and promote acute, neutrophil-dependent glomerular inflammation. In imaging experiments in monocyte reporter <em>Cx3cr1</em>^{<em>gfp/+</em>} mice, co-staining with anti-Ly6B or anti-Ly6C revealed that both non-classical monocytes [CX3 chemokine receptor 1–green fluorescent protein positive (CX3CR1-GFP⁺)] and classical monocytes (CX3CR1-GFP⁺ and Ly6B⁺ or Ly6C⁺) underwent prolonged (&gt;10 minutes) retention and migration in the glomerular microvasculature. On induction of acute glomerulonephritis, these behaviors were increased in classical, but not non-classical, monocytes. Using non-classical monocyte–deficient <em>Csf1r</em>^<em>Cre</em> <em>Nr4a1</em>^{<em>fl/fl</em>} mice, or anti-CCR2 to deplete classical monocytes, the removal of either subset reduced neutrophil retention and activation in acutely inflamed glomeruli, while the depletion of both subsets, via anti-CCR2 treatment in <em>Csf1r</em>^<em>Cre</em> <em>Nr4a1</em>^{<em>fl/fl</em>} mice, led to further reductions in neutrophil activity. In contrast, in a model of CD4⁺ T cell–dependent glomerulonephritis, the depletion of either monocyte subset failed to alter neutrophil responses. These findings indicate that both classical and non-classical monocytes patrol the glomerular microvasculature and promote neutrophil responses in acutely inflamed glomeruli.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 1","pages":"Pages 89-101"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miRNA and mRNA Signatures in Human Acute Kidney Injury Tissue","authors":"Danielle Janosevic ,&nbsp;Thomas De Luca ,&nbsp;Ricardo Melo Ferreira ,&nbsp;Debora L. Gisch ,&nbsp;Ying-Hua Cheng ,&nbsp;Takashi Hato ,&nbsp;Jinghui Luo ,&nbsp;Yingbao Yang ,&nbsp;Jeffrey B. Hodgin ,&nbsp;Carrie L. Phillips ,&nbsp;Pierre C. Dagher ,&nbsp;Kidney Precision Medicine Project,&nbsp;Michael T. Eadon","doi":"10.1016/j.ajpath.2024.08.013","DOIUrl":"10.1016/j.ajpath.2024.08.013","url":null,"abstract":"<div><div>Acute kidney injury (AKI) is an important contributor to the development of chronic kidney disease (CKD). There is a need to understand molecular mediators that drive recovery and progression to CKD. In particular, the regulatory role of miRNAs in AKI is poorly understood. Herein, miRNA and mRNA sequencing were performed on biobanked human kidney tissues obtained during the routine care of subjects with a diagnosis of AKI, minimal change disease, or on nephrectomy tissue with no known kidney disease. mRNA analysis revealed that nephrectomy tissues exhibited an injury signature similar to that of AKI which was not identified in minimal change disease samples. The transcriptomic signature of human AKI was enriched in pathways involved in cell adhesion, epithelial-to-mesenchymal transition, and cell cycle arrest (eg, <em>CDH6, ITGB6, CDKN1A</em>). In AKI, up-regulation of miR-146a, miR-155, miR-142, and miR-122 was associated with pathways involved in immune cell recruitment, inflammation, and epithelial-to-mesenchymal transition. miR-122 and miR-146 were associated with down-regulation of <em>DDR2</em> and <em>IGFBP6</em>, which are genes involved in the recovery and progression of kidney disease. These data provide integrated miRNA signatures that complement mRNA and other epigenetic data available in kidney atlases.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 1","pages":"Pages 102-114"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Deep Learning Approach for Analyzing Glomerular Basement Membrane Lesions in a Mouse Model of X-Linked Alport Syndrome","authors":"Kunio Kawanishi ,&nbsp;Masaki Baba ,&nbsp;Ryosuke Kobayashi ,&nbsp;Ryotaro Hori ,&nbsp;Kentaro Hashikami ,&nbsp;Kenta Danbayashi ,&nbsp;Takako Iwachido ,&nbsp;Mitsuyasu Kato","doi":"10.1016/j.ajpath.2024.10.004","DOIUrl":"10.1016/j.ajpath.2024.10.004","url":null,"abstract":"<div><div>Alport syndrome is a rare kidney disease typically more severe in males due to its X-linked inheritance. However, female patients with heterozygous X-linked Alport syndrome (XLAS) can develop renal failure over time, necessitating accurate pathologic assessment for effective therapy. A key pathologic finding in female patients with XLAS is the mosaic pattern of partial loss of α5 chains of type IV collagen (COL4α5). This study, using a mouse model of XLAS with a nonsense mutation (R471<strong>∗</strong>) in the <em>Col4a5</em> gene, analogous to human XLAS, aimed to examine the consistency of this pattern with the glomerular basement membrane (GBM) structure. A modified periodic acid–methenamine silver staining method was developed for clearer GBM visualization. The integrated images from COL4α5-stained fluorescence, periodic acid–methenamine silver, and low-vacuum scanning electron microscopy into a single-slide section and applied supervised deep learning to predict GBM lesions. Results showed significant individual variability in urinary protein levels and histologic lesions. Pathologic parameters, including crescent formation, focal segmental glomerulosclerosis, and the COL4α5/α2 ratio, correlated with clinical parameters like urinary protein and plasma creatinine levels. Integrated low-vacuum scanning electron microscopy analysis revealed dense GBM regions corresponded to areas where COL4α5 was preserved, whereas coarse GBM (basket-weave lesions) occurred in COL4α5-deficient regions. These advanced techniques can enhance biopsy-based diagnosis of Alport syndrome and aid in developing artificial intelligence diagnostic tools for diseases involving basement membrane lesions.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 1","pages":"Pages 143-154"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Newly Identified Protective Role of C5a Receptor 1 in Kidney Tubules against Toxin-Induced Acute Kidney Injury","authors":"Samuel Mon-Wei Yu ,&nbsp;Emily King ,&nbsp;Miguel Fribourg ,&nbsp;Susan Hartzell ,&nbsp;Liam Tsou ,&nbsp;Logan Gee ,&nbsp;Vivette D. D'Agati ,&nbsp;Joshua M. Thurman ,&nbsp;John Cijiang He ,&nbsp;Paolo Cravedi","doi":"10.1016/j.ajpath.2024.10.003","DOIUrl":"10.1016/j.ajpath.2024.10.003","url":null,"abstract":"<div><div>Acute kidney injury (AKI) remains a major reason for hospitalization with limited therapeutic options. Although complement activation is implicated in AKI, the role of C5a receptor 1 (C5aR1) in kidney tubular cells is unclear. Herein, aristolochic acid nephropathy (AAN) and folic acid nephropathy (FAN) models were used to establish the role of C5aR1 in kidney tubules during AKI in germline <em>C5ar1</em>^{<em>−/−</em>}, myeloid cell–specific, and kidney tubule–specific <em>C5ar1</em> knockout mice. After aristolochic acid and folic acid injection, <em>C5ar1</em>^{<em>−/−</em>} mice had increased AKI severity and a higher degree of tubular injury. Macrophage depletion in <em>C5ar1</em>^{<em>−/−</em>} mice or myeloid cell–specific <em>C5ar1</em> deletion did not affect the outcomes of aristolochic acid–induced AKI. RNA-sequencing data from renal tubular epithelial cells (RTECs) showed that <em>C5ar1</em> deletion was associated with the down-regulation of mitochondrial metabolism and ATP production transcriptional pathways. Metabolic studies confirmed reduced mitochondrial membrane potential at baseline and increased mitochondrial oxidative stress after injury in <em>C5ar1</em>^{<em>−/−</em>} RTECs. Moreover, <em>C5ar1</em>^{<em>−/−</em>} RTECs had enhanced glycolysis, glucose uptake, and lactate production on injury, corroborated by metabolomics analysis of kidneys from AAN mice. Kidney tubule–specific <em>C5ar1</em> knockout mice recapitulated exacerbated AKI observed in <em>C5ar1</em>^{<em>−/−</em>} mice in AAN and FAN. These data indicate that C5aR1 signaling in kidney tubules exerts renoprotective effects against toxin-induced AKI by limiting overt glycolysis and maintaining mitochondrial function, thereby revealing a novel link between the complement system and tubular cell metabolism.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 1","pages":"Pages 126-142"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Single-Cell Sequencing and Spatial Profiling of Kidney Disease","authors":"Amit Verma,&nbsp;Parker C. Wilson","doi":"10.1016/j.ajpath.2024.10.010","DOIUrl":"10.1016/j.ajpath.2024.10.010","url":null,"abstract":"","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 1","pages":"Pages 5-6"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histopathologic Analysis of Human Kidney Spatial Transcriptomics Data","authors":"Pierre Isnard ,&nbsp;Dian Li ,&nbsp;Qiao Xuanyuan ,&nbsp;Haojia Wu ,&nbsp;Benjamin D. Humphreys","doi":"10.1016/j.ajpath.2024.06.011","DOIUrl":"10.1016/j.ajpath.2024.06.011","url":null,"abstract":"<div><div>The application of spatial transcriptomics (ST) technologies is booming and has already yielded important insights across many different tissues and disease models. In nephrology, ST technologies have helped to decipher the cellular and molecular mechanisms in kidney diseases and have allowed the recent creation of spatially anchored human kidney atlases of healthy and diseased kidney tissues. During ST data analysis, the computationally annotated clusters are often superimposed on a histologic image without their initial identification being based on the morphologic and/or spatial analyses of the tissues and lesions. Herein, histopathologic ST data from a human kidney sample were modeled to correspond as closely as possible to the kidney biopsy sample in a health care or research context. This study shows the feasibility of a morphology-based approach to interpreting ST data, helping to improve our understanding of the lesion phenomena at work in chronic kidney disease at both the cellular and the molecular level. Finally, the newly identified pathology-based clusters could be accurately projected onto other slides from nephrectomy or needle biopsy samples. Thus, they serve as a reference for analyzing other kidney tissues, paving the way for the future of molecular microscopy and precision pathology.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 1","pages":"Pages 69-88"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scientific Integrity Policy","authors":"","doi":"10.1016/S0002-9440(24)00436-X","DOIUrl":"10.1016/S0002-9440(24)00436-X","url":null,"abstract":"","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 1","pages":"Pages A11-A14"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143144474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}