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Aberrant membranous localization of cleaved caspase-3 in anaplastic thyroid carcinoma: Implications for cell proliferation and stemness. 半胱天冬酶-3在间变性甲状腺癌中的异常膜定位:对细胞增殖和干性的影响。
IF 2.9 4区 生物学
Histochemistry and Cell Biology Pub Date : 2026-08-27 DOI: 10.1007/s00418-026-02530-5
Ayaka Kashimoto, Noa Fujita, Kazuma Ishida, Kazuki Kanayama, Koichiro Komai, Miyoko Higuchi, Mitsuyoshi Hirokawa, Hiroyuki Ohsaki, Shingo Kamoshida
{"title":"Aberrant membranous localization of cleaved caspase-3 in anaplastic thyroid carcinoma: Implications for cell proliferation and stemness.","authors":"Ayaka Kashimoto, Noa Fujita, Kazuma Ishida, Kazuki Kanayama, Koichiro Komai, Miyoko Higuchi, Mitsuyoshi Hirokawa, Hiroyuki Ohsaki, Shingo Kamoshida","doi":"10.1007/s00418-026-02530-5","DOIUrl":"10.1007/s00418-026-02530-5","url":null,"abstract":"<p><p>Anaplastic thyroid carcinoma (ATC) is among the most aggressive malignancies. Patients with ATC have poor prognoses and require novel therapies. Cleaved caspase-3 (CC3) has pivotal functions in apoptosis and is usually present in the nuclei and cytoplasm of apoptotic cells. We investigated the aberrant membranous localization of CC3 in thyroid carcinoma (TC) and its diagnostic and clinicobiological significance. We examined the expression of nuclear/cytoplasmic CC3 (n/cCC3) and membranous CC3 (mCC3) in 80 primary and one metastatic TC samples. Receiver operating characteristic curve analysis was used to evaluate their diagnostic efficacy for ATC. Multivariate logistic regression analysis was used to identify risk factors for large tumor size. The n/cCC3 and mCC3 indices were significantly greater in ATC than in other types of TC (P < 0.001). Moreover, the area under the curve and sensitivity of mCC3 were greater than those of n/cCC3 for identifying ATC (0.961 versus 0.948 and 95.0% versus 90.0%). A preabsorption test confirmed the specificity of CC3 immunostaining. However, Western blotting indicated that the anti-CC3 antibody crossreacted with an unknown protein with epitopes common to those of CC3. Significant correlations were detected between Ki-67 and n/cCC3 (ρ = 0.536, P < 0.001) and mCC3 (ρ = 0.680, P < 0.001). Multivariate analysis revealed that mCC3 was an independent risk factor for large tumor size. Double immunofluorescence staining demonstrated that mCC3-expressing ATC cells were Ki-67-negative but occasionally SOX2-positive. Our results suggest that mCC3 may have diagnostic value for ATC and that mCC3-expressing ATC cells may be involved in cell proliferation and stemness.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"164 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction: YAP regulates porcine skin-derived stem cells self-renewal partly by repressing Wnt/β-catenin signaling pathway. 更正:YAP部分通过抑制Wnt/β-catenin信号通路调节猪皮肤源性干细胞自我更新。
IF 2.9 4区 生物学
Histochemistry and Cell Biology Pub Date : 2026-08-26 DOI: 10.1007/s00418-026-02507-4
Hong-Chen Yan, Yu Sun, Ming-Yu Zhang, Shu-Er Zhang, Jia-Dong Sun, Paul W Dyce, Francesca Gioia Klinger, Massimo De Felici, Wei Shen, Shun-Feng Cheng
{"title":"Correction: YAP regulates porcine skin-derived stem cells self-renewal partly by repressing Wnt/β-catenin signaling pathway.","authors":"Hong-Chen Yan, Yu Sun, Ming-Yu Zhang, Shu-Er Zhang, Jia-Dong Sun, Paul W Dyce, Francesca Gioia Klinger, Massimo De Felici, Wei Shen, Shun-Feng Cheng","doi":"10.1007/s00418-026-02507-4","DOIUrl":"https://doi.org/10.1007/s00418-026-02507-4","url":null,"abstract":"","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"164 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148827836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The potential of harmaline on triple negative breast cancer: harmaline-DNA interaction related apoptosis, anti-metastasis, and in silico analysis. 盐碱对三阴性乳腺癌的潜在作用:盐碱与dna相互作用相关的凋亡、抗转移和硅分析。
IF 2.9 4区 生物学
Histochemistry and Cell Biology Pub Date : 2026-08-25 DOI: 10.1007/s00418-026-02528-z
Srividya Subramanian, Sai Krishna Guguloth, Sankar Pajaniradje, Suhail Ahmad Bhat, Sathyapriya Chandramohan, A P Vishnumaya, Anjali Suresh Nair, V K Archana, Suci Subramanian, Rukkumani Rajagopalan
{"title":"The potential of harmaline on triple negative breast cancer: harmaline-DNA interaction related apoptosis, anti-metastasis, and in silico analysis.","authors":"Srividya Subramanian, Sai Krishna Guguloth, Sankar Pajaniradje, Suhail Ahmad Bhat, Sathyapriya Chandramohan, A P Vishnumaya, Anjali Suresh Nair, V K Archana, Suci Subramanian, Rukkumani Rajagopalan","doi":"10.1007/s00418-026-02528-z","DOIUrl":"10.1007/s00418-026-02528-z","url":null,"abstract":"<p><p>Breast cancer, particularly triple-negative breast cancer (TNBC), remains a therapeutic challenge owing to limited targeted treatment options and high metastatic potential. This study aimed to investigate the in vitro and in silico anticancer effects of harmaline, a naturally occurring β-carboline alkaloid, against the MDA-MB-231 breast cancer cell line, focusing on its cytotoxic, apoptotic, DNA-binding, and protein interaction potential. Cytotoxicity assessment by MTT assay revealed a significant reduction in cell viability with an IC<sub>50</sub> value of 99.53 µM, further confirmed by LDH release indicating membrane damage. Apoptosis induction was evidenced through Annexin V/PI staining, DNA fragmentation, nuclear condensation, and mitochondrial depolarization. Morphological alterations and wound healing assays demonstrated harmaline's ability to inhibit migration, indicating its anti-migratory activity. Flow cytometry revealed G2/M phase cell cycle arrest, implicating interference with DNA replication and repair processes. Biophysical studies, including ultraviolet-visible (UV-Vis), fluorescence, circular dichroism, FTIR, and KI quenching analyses demonstrated that harmaline interacts with DNA through a mixed binding mode involving both intercalative and groove-associated interactions, leading to conformational alterations in the DNA helix. Complementary molecular docking studies showed harmaline interacting with key cancer-associated proteins with moderate affinity, supporting a multi-target therapeutic mechanism. These results position harmaline as a promising candidate for further preclinical development and structure-based optimization in breast cancer therapy.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"164 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
July in focus in HCB: impact of environmental radiation on cells and tissues. 7月,六氯环己烷:环境辐射对细胞和组织的影响。
IF 2.9 4区 生物学
Histochemistry and Cell Biology Pub Date : 2026-08-25 DOI: 10.1007/s00418-026-02529-y
Douglas J Taatjes, Jürgen Roth
{"title":"July in focus in HCB: impact of environmental radiation on cells and tissues.","authors":"Douglas J Taatjes, Jürgen Roth","doi":"10.1007/s00418-026-02529-y","DOIUrl":"10.1007/s00418-026-02529-y","url":null,"abstract":"","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"164 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
High-sucrose diet induces MMP-9 activation and collagen deposition via oxidative stress in Swiss mice liver. 高糖饮食通过氧化应激诱导瑞士小鼠肝脏MMP-9活化和胶原沉积。
IF 2.9 4区 生物学
Histochemistry and Cell Biology Pub Date : 2026-08-20 DOI: 10.1007/s00418-026-02523-4
Mariana Alves Passos, Juliana Leticia Silva, Túlio César Rodrigues Leite, Isabela Jesus de Deus, Raianne Dos Santos Baleeiro, Rafaella Dhom Ferrari Matos Gomes, Wanderson Geraldo Lima, Carla Speroni Ceron, Sílvia Paula-Gomes
{"title":"High-sucrose diet induces MMP-9 activation and collagen deposition via oxidative stress in Swiss mice liver.","authors":"Mariana Alves Passos, Juliana Leticia Silva, Túlio César Rodrigues Leite, Isabela Jesus de Deus, Raianne Dos Santos Baleeiro, Rafaella Dhom Ferrari Matos Gomes, Wanderson Geraldo Lima, Carla Speroni Ceron, Sílvia Paula-Gomes","doi":"10.1007/s00418-026-02523-4","DOIUrl":"https://doi.org/10.1007/s00418-026-02523-4","url":null,"abstract":"<p><p>Excessive sucrose consumption is associated with various metabolic disorders, including obesity, diabetes, and liver dysfunction. Although oxidative stress is a well-established mechanism contributing to these conditions, its effects on matrix metalloproteinase (MMP) activity in the liver remain poorly understood. This study evaluated the impact of a high-sucrose diet on oxidative stress, MMP-2 and MMP-9 activities, insulin signaling and collagen deposition in the liver of Swiss mice. Male Swiss mice (protocol no. 7,422,050,723) were divided into 2 groups with 16 animals each-control and high-sucrose diet-and were fed for 4 weeks. Liver samples were collected for histomorphological analysis of steatosis, inflammatory infiltrates, and collagen deposition, as well as for biochemical evaluation of antioxidant enzyme activity, oxidative stress markers, MMP activity, and AKT phosphorylated at serine 473. The high-sucrose diet induced metabolic imbalance, steatosis, and inflammatory infiltration, accompanied by oxidative stress in the liver, evidenced by reduced catalase activity (CAT) and glutathione levels (GSH), along with increased protein carbonyls (PCO) and thiobarbituric acid reactive substances (TBARS) levels. Additionally, MMP-9 activity and collagen deposition were higher in mice fed the high-sucrose diet. Notably, AKT phosphorylation at Ser-473 residue was reduced, indicating impaired insulin signaling. These findings suggest that a high-sucrose diet induces hepatic oxidative stress, disrupts insulin signaling, and promotes MMP-9 activation, potentially contributing to liver histopathological changes and dysfunction.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"164 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792370","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}
引用次数: 0
Longitudinal progression of tissue remodeling in experimental pulmonary hypertension is accompanied by a continuously increasing re-expression of extra domain A-containing fibronectin. 实验性肺动脉高压组织重构的纵向进展伴随着含有额外结构域a的纤维连接蛋白的不断增加的再表达。
IF 2.9 4区 生物学
Histochemistry and Cell Biology Pub Date : 2026-08-08 DOI: 10.1007/s00418-026-02516-3
Laura Tempel, Andrea Schrepper, Alexander Berndt, P Christian Schulze, Marcus Franz, Katja Grün
{"title":"Longitudinal progression of tissue remodeling in experimental pulmonary hypertension is accompanied by a continuously increasing re-expression of extra domain A-containing fibronectin.","authors":"Laura Tempel, Andrea Schrepper, Alexander Berndt, P Christian Schulze, Marcus Franz, Katja Grün","doi":"10.1007/s00418-026-02516-3","DOIUrl":"10.1007/s00418-026-02516-3","url":null,"abstract":"<p><p>Pulmonary hypertension (PH) is a progressive disease characterized by pulmonary vascular remodeling and increasing right ventricular (RV) afterload. Extracellular matrix (ECM) remodeling is central to PH, but its temporal dynamics across lung and RV tissue remains insufficiently defined. Extra domain A-containing fibronectin (ED-A<sup>+</sup> Fn) is a fetal fibronectin splice variant re-expressed during tissue injury and chronic inflammation. This study investigated temporal and spatial ED-A<sup>+</sup> Fn expression in monocrotaline (MCT)-induced PH in rats. Male Sprague-Dawley rats were analyzed at day 7, 14, 21, and 28 after MCT injection. Disease progression was assessed by echocardiography, right heart catheterization, histology, immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), and serum enzyme-linked immunosorbent assay (ELISA). MCT induced PH with increasing RV systolic pressure, RV dilatation, reduced tricuspid annular plane systolic excursion (TAPSE), and worsening pulmonary and myocardial tissue damage. ED-A<sup>+</sup> Fn was nearly absent in controls but increased progressively at the protein level in lung and RV tissue. Significant upregulation was detected from day 14 onward in the lung and at later stages in the RV. ED-A<sup>+</sup> Fn was spatially associated with macrophage accumulation and remodeling markers, including α-smooth muscle actin and tenascin-C. By contrast, ED-A<sup>+</sup> Fn messenger RNA (mRNA) levels did not change significantly. Circulating ED-A<sup>+</sup> Fn was increased in PH animals and correlated with impaired RV function, higher RV systolic pressure, and pulmonary and RV myocardial histopathological damage. ED-A<sup>+</sup> Fn is progressively re-expressed during experimental PH and reflects cardiopulmonary remodeling in tissue and circulation. These findings support ED-A<sup>+</sup> Fn as a dynamic biomarker of disease progression and a potential translational target in PH.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"164 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Plectin-mediated mitochondrial fusion is necessary for hepatocellular carcinoma cell migration promoted by higher matrix stiffness. 凝集素介导的线粒体融合是高基质刚度促进肝癌细胞迁移所必需的。
IF 2.9 4区 生物学
Histochemistry and Cell Biology Pub Date : 2026-08-08 DOI: 10.1007/s00418-026-02527-0
Zhihui Wang, Wenbin Wang, Xu Zhang, Qing Luo, Guanbin Song
{"title":"Plectin-mediated mitochondrial fusion is necessary for hepatocellular carcinoma cell migration promoted by higher matrix stiffness.","authors":"Zhihui Wang, Wenbin Wang, Xu Zhang, Qing Luo, Guanbin Song","doi":"10.1007/s00418-026-02527-0","DOIUrl":"10.1007/s00418-026-02527-0","url":null,"abstract":"<p><p>Increased matrix stiffness is a key physical signal affecting the migration of hepatocellular carcinoma (HCC) cells, and mitochondrial dynamics and function also play important roles in cell migration. Plectin may influence mitochondrial dynamics and function through its cytoskeletal cross-linking function. However, the relationship between these two factors remains unclear. HCC cells were seeded on hydrogels with stiffness of 7 kPa and 53 kPa, respectively, to investigate the effects of matrix stiffness on plectin expression, mitochondrial dynamics and function, and cell migration. Moreover, plectin was knocked down to further assess its specific impacts on mitochondrial dynamics and function, as well as cell migration under different matrix stiffness. Compared with 7 kPa, high matrix stiffness (53 kPa) promotes HCC cell migration by upregulating plectin expression, promoting mitochondrial fusion, and enhancing mitochondrial function. Under high matrix stiffness, plectin knockdown weakens mitochondrial fusion capacity and function, reducing cell migration. Subsequently, we treated cells with carbonyl cyanide 3-chlorophenylhydrazone (CCCP) to inhibit mitochondrial function. This treatment significantly suppressed cell migration on high- matrix stiffness. Then, when mitochondrial dynamics were disrupted by the mitochondrial fusion inhibitor 8 (MFI8), mitochondrial function was compromised, and cell migration decreased. High matrix stiffness enhances mitochondrial function by driving mitochondrial fusion through increasing plectin expression, thereby promoting the migration of HCC cells. It provides new insights into the mechanobiological mechanisms underlying matrix stiffness affected HCC cell migration.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"164 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Predominant NR1-positive puncta with limited PSD95 colocalization and close GluA2-EAAT2 apposition in the preBötzinger complex. 在preBötzinger复合体中,主要是nr1阳性点,PSD95共定位有限,GluA2-EAAT2接近。
IF 2.9 4区 生物学
Histochemistry and Cell Biology Pub Date : 2026-08-06 DOI: 10.1007/s00418-026-02521-6
Carol Alejandra Olmos-Pastoresa, Enrique Vázquez-Mendoza, Olivia Vázquez-Martínez, María Leonor López-Meraz, Luis Beltran-Parrazal, Consuelo Morgado-Valle
{"title":"Predominant NR1-positive puncta with limited PSD95 colocalization and close GluA2-EAAT2 apposition in the preBötzinger complex.","authors":"Carol Alejandra Olmos-Pastoresa, Enrique Vázquez-Mendoza, Olivia Vázquez-Martínez, María Leonor López-Meraz, Luis Beltran-Parrazal, Consuelo Morgado-Valle","doi":"10.1007/s00418-026-02521-6","DOIUrl":"10.1007/s00418-026-02521-6","url":null,"abstract":"<p><p>The preBötzinger complex (preBötC) is a medullary network that generates the inspiratory phase of respiratory rhythm in mammals and depends critically on glutamatergic transmission. To characterize the anatomical organization of excitatory signaling elements within this network, we analyzed the distribution, morphology, and colocalization of the AMPA receptor subunit GluA2 and the NMDA receptor subunit NR1, together with the postsynaptic scaffold protein PSD95. We also used immunofluorescence and confocal microscopy to examine the spatial relationship between GluA2-positive puncta and the astrocytic glutamate transporter EAAT2 in the preBötC of adult male rats. NR1-positive puncta were more abundant and densely distributed than GluA2-positive puncta, whereas GluA2-NR1 colocalized puncta constituted only a small fraction of either receptor population. NR1-positive puncta also showed limited colocalization with PSD95-positive puncta, indicating that a substantial fraction of NR1 immunoreactivity is not associated with PSD95-defined postsynaptic domains under the present imaging conditions. In contrast, GluA2-positive puncta displayed a non-random spatial proximity with EAAT2 astrocytic profiles and were frequently located within submicron distances. Together, these findings reveal a spatially differentiated organization of glutamatergic elements in the preBötC, characterized by abundant non-PSD95-associated NR1-positive puncta and close apposition between GluA2-positive puncta and EAAT2-immunoreactive astrocytic profiles. This organization provides an anatomical framework for future studies testing how glutamate receptor localization and glutamate clearance mechanisms contribute to excitability and respiratory rhythm generation and modulation.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"164 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13442488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677333","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}
引用次数: 0
YAP/TEAD complex restricts H3K27ac deposition to suppress testosterone synthesis in adult Leydig cells. YAP/TEAD复合体限制H3K27ac沉积,抑制成体间质细胞的睾酮合成。
IF 2.9 4区 生物学
Histochemistry and Cell Biology Pub Date : 2026-08-05 DOI: 10.1007/s00418-026-02524-3
Zeyu Lin, Shanshan Luo, Mei Zheng, Zihang Lin, Lvjing Luo, Dini Zhang, Xiuli Lian, Xuanyi Wang, Shie Wang, Jiandong Sun
{"title":"YAP/TEAD complex restricts H3K27ac deposition to suppress testosterone synthesis in adult Leydig cells.","authors":"Zeyu Lin, Shanshan Luo, Mei Zheng, Zihang Lin, Lvjing Luo, Dini Zhang, Xiuli Lian, Xuanyi Wang, Shie Wang, Jiandong Sun","doi":"10.1007/s00418-026-02524-3","DOIUrl":"10.1007/s00418-026-02524-3","url":null,"abstract":"<p><p>The Hippo signaling pathway regulates the development of multiple organs, yet its role in the maturation of adult Leydig cells and testosterone synthesis is unclear. In this study, by integrating bulk RNA sequencing and immunohistochemistry, we characterized the spatiotemporal expression patterns of YAP and TEAD family members during postnatal Leydig cell development. Functional assays combining pharmacological inhibition, genetic knockdown, and CUT&Tag-seq analysis were employed to elucidate the underlying mechanisms, and single-cell transcriptomic data from patients with idiopathic non-obstructive azoospermia (iNOA) were analyzed to assess clinical relevance. Results of single-cell transcriptomic analysis revealed that YAP, TEAD1, and TEAD3 are significantly elevated in Leydig cells from patients with iNOA compared with normal controls. In contrast, under normal physiological conditions, YAP protein levels progressively declined during Leydig cell maturation into adulthood, accompanied by increased phosphorylation (p-YAP). Correspondingly, Tead1 and Tead2 are markedly downregulated as immature Leydig cells differentiate into adult Leydig cells. Functional assays further revealed that knockdown of either YAP or TEAD and K975 treatment significantly increased testosterone synthesis and upregulated the expression of Hsd3b6, Cyp17a1, and Hsd17b3. Mechanistically, the YAP/TEAD complex may transcriptionally repress these steroidogenic genes by restricting the deposition of the active histone mark H3K27ac at their promoter regions. Our findings demonstrate that YAP/TEAD orchestrates postnatal Leydig cell maturation by epigenetically repressing the steroidogenic program, revealing a novel role for the Hippo pathway in male reproductive development and providing insights into the pathogenesis of iNOA.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"164 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Endoplasmic reticulum stress is associated with cardiac effects of bisphenol S independently of a high-fat diet. 内质网应激与双酚S对心脏的影响有关,独立于高脂肪饮食。
IF 2.9 4区 生物学
Histochemistry and Cell Biology Pub Date : 2026-08-03 DOI: 10.1007/s00418-026-02525-2
Beatriz Alexandre-Santos, Guilherme Dos Santos Reis, Luiza Mazzali Ferraz, Maria Eduarda Lima da Silva, Gabriel Ferreira Lima, Fernanda Carla Ferreira Brito, Milena Barcza Stockler-Pinto, Antonio Claudio Lucas da Nóbrega, Leandro Miranda-Alves, D'Angelo Carlo Magliano, Eliete Dalla Corte Frantz
{"title":"Endoplasmic reticulum stress is associated with cardiac effects of bisphenol S independently of a high-fat diet.","authors":"Beatriz Alexandre-Santos, Guilherme Dos Santos Reis, Luiza Mazzali Ferraz, Maria Eduarda Lima da Silva, Gabriel Ferreira Lima, Fernanda Carla Ferreira Brito, Milena Barcza Stockler-Pinto, Antonio Claudio Lucas da Nóbrega, Leandro Miranda-Alves, D'Angelo Carlo Magliano, Eliete Dalla Corte Frantz","doi":"10.1007/s00418-026-02525-2","DOIUrl":"10.1007/s00418-026-02525-2","url":null,"abstract":"<p><p>Obesity and endocrine disruptors (EDs) promote endoplasmic reticulum (ER) stress, a mechanism associated with cardiovascular diseases. Among EDs, BPS is widely used in consumer products. Whether BPS promotes cardiac ER stress, either alone or combined with a high-fat diet, remains unclear. Male C57BL/6 mice were assigned to a standard chow diet (SC-15 kJ/g), SC+BPS (SCB), high-fat diet (HF-21 kJ/g), or HF+BPS (HFB), receiving BPS (25 μg/kg/day) through their drinking water for 12 weeks. Body mass (BM), lipid profile, cardiac risk ratio, heart mass, and cardiac ER stress, apoptosis, and oxidative stress markers were assessed. A high-fat diet intake increased BM gain, total cholesterol, cardiac risk ratio, and heart mass compared with standard chow diet intake. These parameters were higher in the SCB group than in the SC group. ER stress (GRP78, ATF4, and CHOP protein expression), pro-apoptotic (BAX protein expression and caspase 3 immunostaining), and pro-oxidative (NOX2 and NOX4 protein expression as well as MDA levels) markers were elevated in high-fat diet-fed animals compared with standard chow-fed animals. BPS exposure increased these parameters in standard chow-fed animals. High-fat diet intake reduced BCL2 expression and increased the BAX/BCL2 ratio compared with standard chow diet intake. BPS exposure increased BCL2 expression in standard chow-fed animals and increased the BAX/BCL2 ratio in high-fat diet-fed animals. ER stress appears to play a role in the cardiac effects of BPS. BPS exposure exacerbated the high-fat diet-induced pro-apoptotic response.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"164 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663745","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}
引用次数: 0
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