{"title":"Lgr5 positive stem cells sustain homeostasis and drive regeneration of the nasal septum olfactory epithelium.","authors":"Suyeon Lee, Hyun-Yi Kim, Jonghoon Choi, Seung-Jun Yoo, Jong-Min Lee, Han-Sung Jung","doi":"10.1007/s00441-026-04060-x","DOIUrl":"10.1007/s00441-026-04060-x","url":null,"abstract":"<p><p>Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5)-expressing cells function as stem cells in various epithelial tissues. However, their specific roles in the olfactory epithelium (OE) are still not well understood. In this study, we aimed to clarify their roles using a genetically modified mouse model that expresses a diphtheria toxin receptor specific to Lgr5 cells. We conducted RNAscope analysis, which confirmed the presence of Lgr5 transcripts throughout the septal OE and revealed their reduction following DT treatment and subsequent reappearance over time. After administering diphtheria toxin, we observe initial epithelial disorganization by day 3, followed by marked thinning by week 1. Regenerative changes are evident by week 4 and continue through week 6. We noted dynamic changes in the markers of basal and progenitor cells. Keratin 14-positive horizontal basal cells became distributed across multiple layers by day 3. SRY-box transcription factor (Sox)2, which is typically expressed in sustentacular and globose basal cells, was confined to the globose basal cells by day 3. However, by week 1, it appeared in multiple layers of the thinned epithelium showing a trend toward its typical localization by week 6. Markers for sensory neurons, cilia, and Bowman's glands exhibited coordinated degeneration followed by ongoing regenerative processes through 6 weeks. Overall, these findings suggest that Lgr5-positive cells are closely associated with epithelial homeostasis and regenerative processes in the olfactory epithelium.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"403 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dmytro Vlasenko, Andrea Maccagno, Adriano Sanna, Tamara Papadakis, Shanjid Ahmed Shiplu, Ramona Schmid, Ulrich Gärtner, Bruno Märkl, Marco Koch, Maryam Keshavarz
{"title":"Histological, ultrastructural, and single-cell profiling reveal immune-mediated remodeling in gallbladder inflammation.","authors":"Dmytro Vlasenko, Andrea Maccagno, Adriano Sanna, Tamara Papadakis, Shanjid Ahmed Shiplu, Ramona Schmid, Ulrich Gärtner, Bruno Märkl, Marco Koch, Maryam Keshavarz","doi":"10.1007/s00441-026-04057-6","DOIUrl":"10.1007/s00441-026-04057-6","url":null,"abstract":"<p><p>Gallbladder inflammation comprises distinct pathological entities, including acute, neutrophil-dominated injury and chronic, fibrotic remodeling. This study aimed to define the cellular and structural programs that characterize these two inflammatory states and link epithelial, immune, and stromal alterations. Tissue and blood samples from forty-one patients, including twelve with acute cholecystitis and twenty-nine with chronic cholelithiasis, were analyzed using histopathology, immunohistochemistry, transmission electron microscopy, targeted cytokine expression analysis, and single-cell RNA sequencing of immune-enriched suspensions. Acute cholecystitis showed epithelial disruption, edema, and dense infiltration by neutrophils and macrophages, including an increased density of CD163<sup>+</sup> macrophages, accompanied by elevated systemic inflammation. Chronic cholelithiasis displayed preserved epithelial continuity, fibrosis, glandular remodeling, and reduced immune-cell density. Ultrastructural analysis revealed abundant mucin granules and intact junctions in acute inflammation, contrasting with mucin depletion and dense-body accumulation in chronic disease. Single-cell transcriptomic analysis identified twelve immune and stromal populations, showing contrasting immune-stromal configurations: pro-inflammatory myeloid and cytotoxic T cells dominated in acute inflammation, whereas macrophage-B-cell-fibroblast networks were enriched in chronic cholelithiasis, reflecting adaptive and fibrotic remodeling rather than a temporal transition. This study defines distinct but coordinated immune-stromal programs underlying human gallbladder inflammation and provides a cellular framework for understanding condition-specific mechanisms of acute and chronic disease.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"403 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12960409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147353605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhongtao Li, Sheng Wang, Diana C Blaydon, David P Kelsell
{"title":"Proteolytic dysregulation in the skin: insight from rare monogenic skin diseases.","authors":"Zhongtao Li, Sheng Wang, Diana C Blaydon, David P Kelsell","doi":"10.1007/s00441-026-04052-x","DOIUrl":"10.1007/s00441-026-04052-x","url":null,"abstract":"<p><p>Proteases are essential enzymes that, through the breakdown of proteins, regulate many aspects of tissue homeostasis including barrier function, cellular signaling, and tissue repair mechanisms in organisms. Disease gene discovery in a number of monogenic skin diseases has deepened the knowledge of how proteases and protease inhibitors can regulate skin homeostasis, keratinocyte desmosome-mediated cell adhesion, and epidermal barrier function. This short review details the association of protease dysregulation with monogenic skin diseases, postulated disease mechanisms, and emerging therapeutic strategies.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"403 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12956936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147347724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sonu Pahal, Arushi Gupta, Vivek Kumar, Prashant Singh, Monu Kaushik, Vishvender Pahal, Geethika Atluri, Amit Chaudhary
{"title":"Brain peptides in Alzheimer's disease - pathophysiology and therapeutic advances.","authors":"Sonu Pahal, Arushi Gupta, Vivek Kumar, Prashant Singh, Monu Kaushik, Vishvender Pahal, Geethika Atluri, Amit Chaudhary","doi":"10.1007/s00441-026-04055-8","DOIUrl":"10.1007/s00441-026-04055-8","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and hallmark neuropathological features, including extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles formed by hyperphosphorylated tau. Peptides occupy a central position in AD pathobiology: pathogenic species such as Aβ oligomers and tau-derived fragments drive synaptic failure, mitochondrial dysfunction, and neuroinflammation, whereas several endogenous neuropeptides exert compensatory neuroprotective, trophic, or homeostatic effects. In parallel, advances in peptide chemistry and structural biology have enabled the design of aggregation inhibitors, receptor-selective neuropeptide analogues, and cell-penetrating or brain-targeted peptide conjugates that modulate key pathways, including proteostasis, insulin and incretin signaling, neurotrophic support, and microglial activation. This review integrates current evidence on how brain peptides contribute to AD pathophysiology, summarizes recent progress in peptide-based therapeutic strategies and delivery platforms, and critically examines the remaining barriers to clinical translation, including blood-brain barrier penetration, metabolic stability, off-target effects, and the need for biomarker-guided patient stratification. By highlighting both mechanistic insights and translational advances, the review article outlines how next-generation engineered peptide therapeutics, used alone or in combination with existing disease-modifying agents, may help reshape the future landscape of AD diagnosis, prevention, and treatment.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"403 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Three-dimensional structure and epithelial changes of the piriform sinus fistula in cotton rats.","authors":"Teppei Nakamura, Marina Hosotani, Osamu Ichii, Takao Irie, Akio Shinohara, Hirokazu Kouguchi, Yasuhiro Kon","doi":"10.1007/s00441-026-04056-7","DOIUrl":"10.1007/s00441-026-04056-7","url":null,"abstract":"<p><p>Piriform sinus fistula (PSF) is a rare congenital anomaly derived from the third or fourth pharyngeal pouch. However, its developmental mechanisms remain poorly understood owing to the absence of suitable animal models. Cotton rats (Sigmodon hispidus) spontaneously develop PSF, providing a unique opportunity to investigate its anatomical origin and postnatal remodeling. In this study, we performed a three-dimensional reconstruction of serial histological sections from two inbred strains, HIS/Mz with third-pouch-derived PSF and HIS/Hiph with fourth-pouch-derived PSF. The third-pouch PSF opened dorsally at the base of the piriform sinus and terminated outside the thyroid gland, whereas the fourth-pouch PSF opened ventrally at the apex and extended into the thyroid parenchyma. Focusing on the fourth-pouch PSF in the HIS/Hiph, we further identified progressive epithelial stratification and age-dependent inflammation leading to suppurative thyroiditis. This remodeling was accompanied by marked alterations in epithelial marker expression, including a shift from Nkx2-1<sup>+</sup>/CK8<sup>+</sup>/UEA-I<sup>-</sup> to p63<sup>+</sup>/CK5<sup>+</sup>/UEA-I<sup>+</sup> cell populations. Together, these features resemble the known characteristics of ultimobranchial body remnants and highlight the dynamic inflammation-associated transformation of the PSF epithelium. Collectively, our findings establish the cotton rat as a biologically informative experimental animal model for elucidating the developmental origin and pathological progression of PSF. This study provides new insights that may improve understanding, diagnosis, and clinical management of congenital cervical anomalies in humans.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"403 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147289396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"TGFβ signaling regulates Col15a1 expression in fenestrated endothelial cells of the rat pituitary.","authors":"Takashi Nakakura, Takehiro Tsukada, Takeshi Suzuki","doi":"10.1007/s00441-026-04059-4","DOIUrl":"10.1007/s00441-026-04059-4","url":null,"abstract":"<p><p>Fenestrated capillaries in the anterior lobe (AL) of the pituitary gland are specialized for efficient hormone exchange and are surrounded by extracellular matrix-rich basement membranes (BMs). Although several collagens have been implicated in the structural regulation of capillaries in the pituitary, the contribution of collagen XV remains unknown. In the present study, we investigated the expression, localization, and regulation of COL15A1, the α1 chain of collagen XV, in the rat pituitary. Real-time quantitative PCR (RT-qPCR) revealed that Col15a1 is highly expressed in the endothelial cell fraction isolated from rat AL. In situ hybridization showed that Col15a1 is expressed in plasmalemma vesicle-associated protein (PLVAP)-positive fenestrated endothelial cells in the AL. Immunohistochemistry demonstrated that COL15A1 is localized to BMs surrounding PLVAP-positive fenestrated capillaries in the AL, the median eminence, and the choroid plexus, but not in those surrounding continuous capillaries in the cerebrum. Because transforming growth factor-β (TGFβ) is a key regulator of collagen expression, we examined its role in Col15a1 regulation. RT-qPCR and in situ hybridization revealed that Tgfbr2 is expressed in fenestrated endothelial cells in the AL. Immunocytochemistry demonstrated that TGFβ1 stimulation induces nuclear translocation of SMAD2 in cultured endothelial cells isolated from the rat AL. RT-qPCR also showed that TGFβ1 significantly increases Col15a1 expression, which is suppressed by the TGFβ receptor I inhibitor SB431542. Together, these results demonstrate that TGFβ signaling regulates Col15a1 expression in fenestrated endothelial cells and suggest that collagen XV contributes to the structural and functional specialization of fenestrated capillaries in the pituitary.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"403 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Wójtowicz, Agnieszka Sadowska, Kamil Myszczyński, Tomasz Molcan, Monika M Kaczmarek, Anna Szóstek-Mioduchowska
{"title":"Interleukin-4 changes the transcriptome, ECM-associated components and function of mare endometrial fibroblast: Insights from healthy and fibrotic cells.","authors":"Anna Wójtowicz, Agnieszka Sadowska, Kamil Myszczyński, Tomasz Molcan, Monika M Kaczmarek, Anna Szóstek-Mioduchowska","doi":"10.1007/s00441-026-04049-6","DOIUrl":"10.1007/s00441-026-04049-6","url":null,"abstract":"<p><p>Fibrosis remains incompletely understood, particularly in terms of how immune mediators shape stromal programs. We used a spontaneous large‑animal model-endometrosis (equine endometrial fibrosis) to define how interleukin‑4 (IL‑4) reprograms fibroblasts from healthy and fibrotic endometrium. Primary fibroblasts were exposed to IL‑4 (10 ng/mL) for 48 or 96 h. At 48 h, bulk transcriptomes revealed 1307 differentially expressed genes (DEGs; 648 up, 659 down) and 1271 DEGs (645 up, 626 down) in fibroblasts derived from endometria without or with endometrosis, respectively. Enrichment analyses implicated cellular metabolism, extracellular matrix (ECM) organization and remodeling, and signaling pathways commonly linked to fibrogenesis. IL‑4 also affected the long non‑coding RNA (lncRNA) expression, with 143 and 135 differentially expressed lncRNAs in fibroblasts derived from healthy or fibrotic endometria, respectively; linking these lncRNAs to DEGs involved in inflammation, ECM organization, and cytokine signaling. Moreover, IL‑4 increased proliferation and viability in fibroblasts derived from healthy or fibrotic endometria, while selectively reducing migration in fibroblasts derived from endometria without fibrosis after 96 h. IL‑4 further altered mRNA expression, protein abundance, and gelatinolytic activity of matrix metalloproteinases in a manner contingent on the fibrosis status of the tissue of origin, indicating stage‑dependent control of ECM turnover. Collectively, these data identify IL‑4 as a potent modulator of fibroblast function in a spontaneous large‑animal fibrosis model, revealing fibrosis stage‑dependent responses.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"403 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147269662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bandana Rana, Elina Pokharel, Je-Hee Jang, Jae-Hee Lee, Hitoshi Yamamoto, Ji-Youn Kim, Eui-Kyun Park, Wern-Joo Sohn, Seo-Young An, Chang-Hyeon An, Young-Eun Kwon, Youngkyun Lee, Jae-Kwang Jung, Jung-Hong Ha, Jae-Young Kim
{"title":"MG132 facilitates dentin regeneration by modulating inflammation and odontoblast differentiation.","authors":"Bandana Rana, Elina Pokharel, Je-Hee Jang, Jae-Hee Lee, Hitoshi Yamamoto, Ji-Youn Kim, Eui-Kyun Park, Wern-Joo Sohn, Seo-Young An, Chang-Hyeon An, Young-Eun Kwon, Youngkyun Lee, Jae-Kwang Jung, Jung-Hong Ha, Jae-Young Kim","doi":"10.1007/s00441-026-04051-y","DOIUrl":"10.1007/s00441-026-04051-y","url":null,"abstract":"<p><p>Although regeneration of the dentin-pulp complex is a key goal in endodontic therapy, pulpal inflammation can impede effective tissue repair and sustained healing. Recent studies suggest that proteasome inhibitors can modulate key cellular processes involved in tissue regeneration. MG132 (carbobenzoxy-Leu-Leu-leucinal) is a reversible proteasome inhibitor used in experimental settings to study these mechanisms, although its efficacy in in vivo models of dental tissue regeneration remains unclear. In this study, we investigated the effects of MG132 in modulating inflammation and regenerating dentin using a murine pulp exposure model. Involved signaling pathways were examined using in vitro-cultivated human dental pulp stem cells (hDPSCs). MG132 was then locally administered into exposed pulp cavities. Inflammation, cellular differentiation, and hard tissue formation were assessed using histological staining, immunohistochemistry, and micro-computed tomography, respectively. Following MG132 treatment of hDPSCs, RT-qPCR revealed the elevated expression of Wnt signaling-related molecules involved in dentin formation. At day 5 of treatment, MG132 significantly reduced the expression of inflammatory markers, including myeloperoxidase, F4/80, nuclear factor kappa B, and tumor necrosis factor-alpha, indicating attenuation of early excessive inflammatory responses. In addition, treatment enhanced odontoblast differentiation and mineralization, as evidenced by the upregulated expression of Nestin, collagen type I alpha-1, transforming growth factor beta 1, runt-related transcription factor 2, osteopontin, and osteocalcin. Moreover, at 42 days, MG132-treated samples exhibited distinct dentin bridge formation.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"403 2","pages":"24"},"PeriodicalIF":3.1,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146225660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Harry Scott, Li Dong, Andrew Stevenson, Patricia E Martin, Sheila V Graham
{"title":"The relationship between Connexin 43 (Cx43) and partner protein, human discs large homologue-1 (Dlg1) during wound closure in keratinocytes.","authors":"Harry Scott, Li Dong, Andrew Stevenson, Patricia E Martin, Sheila V Graham","doi":"10.1007/s00441-025-04030-9","DOIUrl":"10.1007/s00441-025-04030-9","url":null,"abstract":"<p><p>Plasma membrane gap junctions, formed by connexin proteins, are responsible for direct intercellular communication between adjacent cells by allowing the exchange of ions, metabolites, secondary messengers and microRNAs. Connexin 43 (Cx43) is a widely expressed gap junction protein. Cx43 mis-expression is associated with various disease states, including chronic non-healing wounds. Loss of Cx43 from the plasma membrane is important to allow wound resolution. Cx43 expression increases, and gap junctions reform, upon wound closure. Cx43 directly interacts with Dlg1, a membrane-associated guanylate kinase (MAGUK) protein, which controls cell shape and polarity. In this study, AlphaFold3 modelling predicted an interaction between amino acids 263-269 and 302-320 of Cx43 and the SH3, HOOK and GUK domains of Dlg1. Since Dlg1 is required for maintaining Cx43 protein levels at the plasma membrane, we hypothesised that Dlg1 may regulate wound healing via its functional interaction with Cx43. Cx43 and Dlg1 relocated to the cytoplasm of cells at the wound edge in scrape wound assays and co-located in pseudopodia of cells migrating towards the wound edge in live cell imaging experiments. Scratch wound assays carried out in HaCaT cells treated with siRNA targeting Dlg1 showed that Dlg1 depletion resulted in reduced wound closure rates. This was not due to changes in cell migration, suggesting that Dlg1 controlled cell proliferation. The data demonstrate that Cx43 and Dlg1 both contribute to wound closure, but that Dlg1 has other crucial functions in migrating cells separate from its role in maintaining Cx43 at the plasma membrane.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"403 2","pages":"23"},"PeriodicalIF":3.1,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12913269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146212238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hydrogen peroxide reduces Cx40, Cx43, and Cx45 gap junction function.","authors":"Yi X Li, Donglin Bai","doi":"10.1007/s00441-026-04047-8","DOIUrl":"10.1007/s00441-026-04047-8","url":null,"abstract":"<p><p>Cardiac gap junctions (GJs), formed by connexin 40 (Cx40), Cx43, and Cx45, are essential for the rapid propagation of action potentials in the myocardium, which synchronizes the atria and ventricles to produce a rhythmic heartbeat. Oxidative stress is characterized by elevated levels of reactive oxygen species (ROS) and is a known contributor to cardiac arrhythmias. However, it is not clear whether the proarrhythmic action of ROS is linked to its modulation of cardiac GJs among other membrane channels. Here, we investigated the acute effects of hydrogen peroxide (H₂O₂), an ROS, on the function of cardiac GJs expressed in genetically engineered human embryonic kidney (HEK293) cells with dual whole-cell patch clamp recordings. We found that H₂O₂ significantly reduced the probability of cell pairs showing GJ coupling and the coupling conductance (G<sub>j</sub>) for Cx45, Cx43, and Cx40 GJs. Single channel conductance (γ<sub>j</sub>) for both Cx40 and Cx43 GJs was found to be significantly reduced, while the transjunctional voltage-dependent gating (V<sub>j</sub>-gating) of all cardiac GJs remained unaffected. Our data demonstrate that one of the key ROS (H<sub>2</sub>O<sub>2</sub>) could reduce cardiac GJ function, which could be an independent factor to promote cardiac arrhythmias.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"403 2","pages":"22"},"PeriodicalIF":3.1,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146206622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}