Victor E Arana-Chavez, Vivian Bradaschia-Correa, Isabella Z Guiati, Leticia S Castro-Filice
{"title":"Proteoglycans and Biomineralization of Bone and Dentin.","authors":"Victor E Arana-Chavez, Vivian Bradaschia-Correa, Isabella Z Guiati, Leticia S Castro-Filice","doi":"10.1369/00221554261478974","DOIUrl":"10.1369/00221554261478974","url":null,"abstract":"<p><p>Although many advances have been made during the last six decades, the controlled processes by which vertebrate hard tissues acquire, organize, and maintain their mineral component remain only partially understood. Mineralized tissues can be classified into two categories based on their developmental origin. Enamel is the only hard tissue of epithelial origin; all other hard tissues are of connective tissue origin and therefore possess a collagen-rich extracellular matrix as their main organic component. The cells responsible for the formation of collagen-based hard tissues regulate the synthesis and degradation of non-collagenous components, among which proteoglycans (PGs) play a key role in biomineralization. This review focuses on the mineralization process of bone and dentin, highlighting the highly coordinated sequential events leading to the acquisition of the mineral phase. Initially, the forming cells release numerous small spherical membrane-limited bodies known as matrix vesicles (MVs), which constitute the nanocompartments necessary for the onset of mineral nucleation (vesicular stage). At this stage, extracellular matrix PGs bind to the MV membrane and subsequently to calcium ions, thereby allowing the accumulation of high concentrations of calcium around the MVs. Following PG degradation, calcium ions enter the MVs through annexin channels, leading to the nucleation and growth of the first mineral crystals. Subsequently, cells orchestrate the conditions required for mineral propagation into the surrounding collagenous matrix (fibrillar stage). During this phase, PGs and other non-collagenous matrix components play a crucial role in promoting mineralization progression as well as in limiting and interrupting the process.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":" ","pages":"221554261478974"},"PeriodicalIF":1.5,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katharina Landmann, Florian Bartenschlager, David Meierhofer, Andreas Spree, Caroline Pisch, Annette Zeyner, Christiane L Schnabel, Lars Mundhenk
{"title":"Ortholog-specific Spatial Expression of Vanins in the Respiratory Tract of Horses.","authors":"Katharina Landmann, Florian Bartenschlager, David Meierhofer, Andreas Spree, Caroline Pisch, Annette Zeyner, Christiane L Schnabel, Lars Mundhenk","doi":"10.1369/00221554261474565","DOIUrl":"10.1369/00221554261474565","url":null,"abstract":"<p><p>Equine asthma (EA) is the most prevalent chronic respiratory disease in horses, but molecules thought to be relevant in its pathogenesis are not yet fully understood. Recently, increased Vanin-1 (VNN1) levels were found in bronchoalveolar lavage fluid from horses with severe EA. Human VNN1 is known as a pantetheinase, which is associated with respiratory diseases such as asthma, but the equine vanins (eVNNs) are uncharacterized. We identified the domain architecture of eVNN in silico and analyzed its tissue expression in healthy horses using RT-PCR (<i>n</i>=5) and in situ hybridization (<i>n</i>=3). Recombinant eVNNs were expressed in HEK293 cells to assess cellular transport and glycosylation via Endo H and PNGase F treatment. Three putative functional <i>eVNNs</i> were identified on chromosome 10, each containing canonical Nitrilase superfamily domains. All genes showed a broad tissue expression, but distinct airway localization: <i>eVNN1</i> and <i>eVNN2</i> were predominantly expressed in respiratory epithelium, whereas <i>eVNN3</i> was localized in submucosal glands. eVNN1 and eVNN3 were secreted, while eVNN2 remained cell associated. Pantetheinase activity of recombinant eVNN1 was confirmed by mass spectrometry. The three eVNNs appear to cover different functional niches in equine airways, enabling future research into their putative role in EA.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":" ","pages":"221554261474565"},"PeriodicalIF":1.5,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13530036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immunohistochemical Characterization of Keratan Sulfate Preferentially Expressed in Papillary Thyroid Carcinoma Using a Novel Monoclonal Antibody 299-1C1.","authors":"Eiichi Kato, Tomoya O Akama, Natsumi Yonemoto, Akifumi Muramoto, Shigeharu Fujieda, Motohiro Kobayashi","doi":"10.1369/00221554261479793","DOIUrl":"10.1369/00221554261479793","url":null,"abstract":"<p><p>Keratan sulfate (KS) is a glycosaminoglycan consisting of repeating <i>N</i>-acetyllactosamine disaccharides, in which both galactose and <i>N</i>-acetylglucosamine are often 6-<i>O</i>-sulfated. It has been reported that KS recognized by the monoclonal antibodies 5D4 and 373E1 is preferentially expressed in papillary thyroid carcinoma (PTC) and only minimally in other thyroid tumors/lesions or normal thyroid tissue. However, the precise epitopes recognized by these antibodies remain incompletely characterized, and the expression and extent of low-sulfated KS in PTC have not been systematically evaluated. To better understand the nature of KS expressed in PTC, we generated a novel anti-KS monoclonal antibody, 299-1C1, and performed immunohistochemical analyses using 299-1C1 together with two existing anti-KS monoclonal antibodies, 5D4 and R-10G, in combination with keratanase II and endo-β-galactosidase. The results showed that both highly sulfated and low-sulfated KS are preferentially expressed in PTC, including lymph node metastases, accompanied by upregulation of genes encoding key KS biosynthetic enzymes (<i>B3GNT7</i>, <i>B4GALT4</i>, <i>CHST2</i>, and <i>CHST6</i>) in integrated TCGA/GTEx transcriptomic datasets. Expression of <i>B3GNT7</i>, <i>B4GALT4</i>, and <i>CHST2</i>, but not <i>CHST6</i>, was further increased in <i>BRAF</i>-mutant PTCs. These findings indicate that anti-KS monoclonal antibodies are useful for the pathological diagnosis of PTC, particularly for distinguishing lymph node metastases from intranodal thyroid inclusions.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":" ","pages":"221554261479793"},"PeriodicalIF":1.5,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13525095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of EXT Family Enzymes in Heparan Sulfate Biosynthesis.","authors":"Digantkumar Chapla, Kelley W Moremen","doi":"10.1369/00221554261479792","DOIUrl":"10.1369/00221554261479792","url":null,"abstract":"<p><p>Heparan sulfate (HS) proteoglycans are essential regulators of cell signaling, development, and extracellular matrix organization. Central to the HS biosynthesis pathway is the exostosin family of enzymes that control commitment to HS assembly and catalyze formation of the polymer backbone in the Golgi apparatus. Recent structural studies have substantially revised our understanding by demonstrating that the HS co-polymerase is a tightly organized EXT1-EXT2 heterodimer, wherein the GT-B domain of EXT1 and the GT-A domain of EXT2 provide the β1,4-GlcA and α1,4-GlcNAc transferase activities, respectively. Parallel work on EXTL3 clarified how selective recognition of the linker-region glycopeptide commits to HS extension, outcompeting the default chondroitin sulfate pathway. In contrast, EXTL2 is best viewed as a regulatory GlcNAc transferase that can cap or divert linker intermediates rather than as a polymerase, whereas EXTL1 remains the least defined family member despite evidence for GlcNAc transferase activity. Genetic studies continue to reveal their importance in human disease, including hereditary multiple exostoses and EXTL3-associated immunodeficiency. Despite this progress, major questions remain regarding chain length control, enzyme coordination, and therapeutic targeting. This short review integrates recent structural, biochemical, and genetic advances to provide an updated narrative of how mammalian EXT proteins govern HS biosynthesis.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":" ","pages":"221554261479792"},"PeriodicalIF":1.5,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Arthur Morley-Bunker, Georgia Turner, Brooke Beardsley, Helen Morrin, John Pearson, Logan C Walker, Margaret Currie
{"title":"Detection of Human Cytomegalovirus <i>lncRNA4.9</i> in Breast Tumor Tissue Using RNA In Situ Hybridization.","authors":"Arthur Morley-Bunker, Georgia Turner, Brooke Beardsley, Helen Morrin, John Pearson, Logan C Walker, Margaret Currie","doi":"10.1369/00221554261474562","DOIUrl":"https://doi.org/10.1369/00221554261474562","url":null,"abstract":"<p><p>Human cytomegalovirus (HCMV) has been linked to tumor progression in several cancers, but its role in breast cancer remains uncertain. This study investigated HCMV long non-coding RNA4.9 (<i>lncRNA4.9</i>) in three breast cancer subtypes (ER+/PR+, <i>n</i>=25; HER2-positive <i>n</i>=24; triple-negative, <i>n</i>=26) and normal breast tissue (<i>n</i>=5) using RNAscope. Serum HCMV IgG and IgM levels were measured, and immunohistochemistry was used to assess the pan-macrophage marker CD68 in breast tissue. HCMV IgG seropositivity was more common in ER+ patients, while IgM positivity was more frequent in HER2-positive and triple-negative cases. HCMV <i>lncRNA4.9</i> signals were detected in over half of tumor samples, localizing to invasive tumor cells, stromal cells, adipose tissue, and ductal carcinoma in situ (DCIS). Although detection rates did not differ significantly between breast cancer subtypes, triple-negative tumors exhibited mid- to high-level <i>lncRNA4.9</i> expression. Immunohistochemical analysis demonstrated CD68+ cells present in most tumors and were more abundant in HCMV <i>lncRNA4.9</i>-positive samples. These cells co-localized with <i>lncRNA4.9</i>-positive cells at invasive margins, while in associated foci of DCIS, CD68+ cells were present in surrounding stroma. This study provides the first demonstration of HCMV <i>lncRNA4.9</i> in breast tissue and supports HCMV's potential role in the biology of a subset of breast cancers.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":" ","pages":"221554261474562"},"PeriodicalIF":1.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immunocytochemical Localization of Neuronal Nitric Oxide Synthase (nNOS) in Neutrophils: Hydroxyurea Therapy Induced Nucleo-Cytoplasmic Translocation in Sickle Cell Disease.","authors":"Rashmi Saini, Shilpy Shakya, Silvio Roberto Consonni","doi":"10.1369/00221554261462592","DOIUrl":"https://doi.org/10.1369/00221554261462592","url":null,"abstract":"<p><p>Sickle cell disease (SCD) is an inherited hemoglobinopathy leading to the deformability of red blood cells, enhanced cellular adhesion, and blockage in microcirculation. \"Sickle Neutrophils\" cause oxidative stress and decreased bioavailability of nitric oxide (NO) due to enhanced generation of reactive oxygen species (ROS). The mechanism of action of the common medication of SCD, hydroxyurea (HU), has not yet been thoroughly examined. This investigation examines the subcellular localization of neuronal nitric oxide synthase (nNOS) using immunoelectron microscopy, and confocal microscopy, as well as NO production and ROS generation by flow cytometry in neutrophils from steady-state SCD patients, and SCD patients on HU therapy. nNOS was increased and prominently distributed in the cytoplasmic compartment, with no nNOS staining in the nucleus of neutrophils in SCD-HU patients. ROS was found to be increased in SCD patients and was significantly reduced after HU treatment. An increase in NO production and decrease in ROS are linked to nNOS's nucleo-cytoplasmic shuttling in SCD neutrophils after HU therapy that provides a novel cellular mechanism through which HU regulates neutrophil function. In conclusion, this study establishes for the first time that HU therapy induces a favorable nucleo-cytoplasmic translocation of nNOS in SCD neutrophils, indicating a key mechanism behind the therapeutic effectiveness of HU in SCD.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":" ","pages":"221554261462592"},"PeriodicalIF":1.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13486396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neutrophil Extracellular Traps Formation Adhering to Cholesterol Crystals Modulates Inflammatory Cytokines Release and Promotes Their Disruption: Insights In Situ Touch-imprints Method From Non-obstructive General Angioscopy.","authors":"Chikao Yutani, Nobuzo Iwa, Hirotaka Noda, Manabu Kobayashi, Satoru Takahashi, Mitsuhiko Takewa, Sei Komatsu, Tomoki Ohara, Kazuhisa Kodama","doi":"10.1369/00221554261473330","DOIUrl":"10.1369/00221554261473330","url":null,"abstract":"<p><p>Both macrophages and neutrophils are recognized as innate immune cells; the former engulf cholesterol crystals (CCs) while secreting NLRP3, which also promote inflammatory responses and drive the latter into atherosclerotic plaques. Moreover, recent studies have implied a critical role of NLRP3 in neutrophil recruitment into atherosclerotic lesions as neutrophil extracellular traps (NETs), which have not been visualized in vivo adhering on CCs so far. We have observed that neutrophils simultaneously attracted by NLRP3 cause NETs formation in situ from spontaneously ruptured atherosclerotic plaques by using touch-imprints method. This study aimed to confirm by imaging that NETs react to CCs, release NLRP3-related inflammatory factor, and degenerate on the surfaces that might result in breakages. These findings raise the possibility that NET-forming neutrophils not only respond to CCs but may also contribute to their structural modification or fragmentation. Such interactions may represent a previously underappreciated bidirectional relationship between CCs and NETs in human atherothrombosis.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":" ","pages":"221554261473330"},"PeriodicalIF":1.5,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13442907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abderrahman Ouban, Amani Alkofide, Antonello Podda, Awatif Eid Alanazi, Nader Ashraf, Tarek Ziad Arabi, Belal Nedal Sabbah, Katherine Elston, Vijay Baichwal, Erin Rudzinski, Eleanor Y Chen, Nya D Nelson, Catherine Albert, Atif A Ahmed
{"title":"Spatial Proteomic Profiling, a Novel Method for Detecting Diagnostic and Prognostic Proteins in Pediatric Sarcoma.","authors":"Abderrahman Ouban, Amani Alkofide, Antonello Podda, Awatif Eid Alanazi, Nader Ashraf, Tarek Ziad Arabi, Belal Nedal Sabbah, Katherine Elston, Vijay Baichwal, Erin Rudzinski, Eleanor Y Chen, Nya D Nelson, Catherine Albert, Atif A Ahmed","doi":"10.1369/00221554261455962","DOIUrl":"10.1369/00221554261455962","url":null,"abstract":"<p><p>Pediatric sarcomas comprise approximately 10% of all childhood solid malignancies and are characterized by distinct genetic and proteomic alterations that have potential diagnostic, prognostic, and therapeutic significance. We have utilized digital spatial profiling (DSP) to identify protein expression in pediatric Ewing sarcoma (ES), Osteosarcoma (OS), Alveolar rhabdomyosarcoma (ARMS), and Embryonal rhabdomyosarcoma (ERMS), in association with clinical outcomes. Formalin-fixed, paraffin-embedded sections from a tissue microarray block containing eight ES, eight OS, five ARMS, and three ERMS cases were subjected to proteomic DSP on a GeoMx NanoString platform yielding information on expression of 580 proteins. Proteins related to epigenetic regulation, signaling pathways, and mesenchymal differentiation were broadly expressed across all tumor types. Tumor-specific protein profiles were defined based on highly expressed proteins. Differentially expressed proteins include Cyclin D1 in ES, S100A4 in OS and IKKi/IKKe in ARMS and ERMS. Immunohistochemical validation confirmed variable expression of H3K27me3 across the tumors, and elevated expression of Cyclin D1 in ES and S100 in OS. These findings underscore the utility of DSP as a high-resolution proteomic tool for the identification of clinically relevant biomarkers in pediatric sarcomas. The results provide a foundation for further investigation of candidate proteins with potential diagnostic, prognostic, and therapeutic applications.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":" ","pages":"221554261455962"},"PeriodicalIF":1.5,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13350073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148411858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Manula S B Rathnayake, Reimer V Wolff, Nicole Kops, Karyna Kulakova, Gerjo J V M van Osch, Brooke Farrugia, Kathryn S Stok
{"title":"Expression and Spatial Localization of Glycosaminoglycan Types in Cartilage From Different Anatomical Locations.","authors":"Manula S B Rathnayake, Reimer V Wolff, Nicole Kops, Karyna Kulakova, Gerjo J V M van Osch, Brooke Farrugia, Kathryn S Stok","doi":"10.1369/00221554261460112","DOIUrl":"10.1369/00221554261460112","url":null,"abstract":"<p><p>Sulphated glycosaminoglycan (sGAG) is a major component of cartilage and known to be involved in cell signaling processes, but little is known about expression and localization in different cartilage types. Using common histochemical staining methods to assess regional sGAG distribution in bovine articular, meniscal, auricular, and nasal cartilage, different staining patterns were found for alcian blue, Safranin O and thionine. Immunohistochemistry to identify expression and location of different epitopes of chondroitin sulfate (C-0-S, C-4-S and C-6-S), dermatan sulfate, keratan sulfate, and heparan sulfate, also demonstrated regional differences which could not explain the differences in histochemical staining. Chondroitin sulfate and keratan sulfate were expressed in all cartilage types investigated, however keratan sulfate was not expressed in the superficial zone of articular cartilage. Dermatan sulfate was only present in tensile load-bearing zones of articular and meniscal cartilage, and in the perichondrium of auricular and nasal cartilage. Despite being hyaline, nasal cartilage and articular cartilage showed dissimilar sGAG expressions. In conclusion, sGAG localization in different types of cartilage is distinctly different, suggesting diverse structural and mechanical functions governed by GAGs. These differences are important for our understanding of the role of sGAG in cartilage function and in cartilage tissue engineering strategies.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":" ","pages":"221554261460112"},"PeriodicalIF":1.5,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13331793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alfonso Cepeda-Emiliani, Tomás García-Caballero, María Otero-Alén, Juan Suárez-Quintanilla, Marina Gándara-Cortés, Rosalía Gallego, Lucía García-Caballero
{"title":"Aquaporin-4 Localization in Terminal Glial Cells of Human Mechanosensory Corpuscles: An Immunohistochemical Study of Penile Tissues.","authors":"Alfonso Cepeda-Emiliani, Tomás García-Caballero, María Otero-Alén, Juan Suárez-Quintanilla, Marina Gándara-Cortés, Rosalía Gallego, Lucía García-Caballero","doi":"10.1369/00221554261454417","DOIUrl":"10.1369/00221554261454417","url":null,"abstract":"<p><p>Aquaporin-4 (AQP4), the predominant water channel in the central nervous system, has been extensively characterized in astroglia, but its presence in peripheral mechanoreceptive end-organs remains unknown. We investigated AQP4 localization in human mechanosensory corpuscles using formalin-fixed, paraffin-embedded penile tissues from 11 adult cadavers and 12 surgical prepuces. Single and double immunohistochemistry was performed in serial sections with a comprehensive battery of antibodies targeting axons (neurofilaments, neuron-specific enolase [NSE], protein gene product 9.5 [PGP9.5], synaptophysin), glial cells (S100, nestin, nerve growth factor receptor [NGFR], vimentin, Wilms' tumor 1 [WT1], growth-associated protein 43 [GAP43]), perineurial and endoneurial cells (α-smooth muscle actin [α-SMA], epithelial membrane antigen [EMA], glucose transporter 1 [Glut-1], CD34), and extracellular matrix components (collagen type IV [COLIV]). AQP4 immunoreactivity was consistently observed in the terminal glial cells (TGCs) of all types of mechanosensory corpuscles across all penile regions examined, including Meissner, genital, Krause, and Pacinian corpuscles. Outer-core lamellar cells of Pacinian corpuscles also exhibited AQP4 expression. The AQP4<sup>+</sup> mechanosensory corpuscles exhibited immunohistochemical profiles consistent with the established marker patterns of sensory corpuscles (S100<sup>+</sup>/WT1<sup>+</sup>/vimentin<sup>+</sup>/nestin<sup>+</sup>/Gap-43<sup>+</sup>/NGFR<sup>+</sup> TGCs; synaptophysin<sup>+</sup>/neurofilaments<sup>+</sup>/PGP9.5<sup>+</sup>/NSE<sup>+</sup> axons; CD34<sup>+</sup> intermediate layer; EMA<sup>+</sup>/Glut-1<sup>+</sup>/vimentin<sup>+</sup>/COLIV<sup>+</sup>/NGFR<sup>+</sup>/Gap-43<sup>+</sup> outer core; COLIV<sup>+</sup> extracellular matrix). Beyond sensory corpuscles, AQP4 was present in Schwann cells of nerve bundles and inconsistently in vascular endothelium. These findings provide the first evidence that AQP4 is a molecular constituent of TGCs in human mechanosensory corpuscles, suggesting roles in local water-ion homeostasis or other non-transporting functions of AQP4, and warranting further investigation of its biological significance in low-threshold mechanoreceptor end-organs.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":" ","pages":"221554261454417"},"PeriodicalIF":1.5,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13331794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}