Zinhle P Mlambo, Motshedisi Sebitloane, Thajasvarie Naicker
{"title":"Immunoexpression of placental growth factor (PlGF) and soluble FMS-like tyrosine kinase 1 (sFlt-1) in the placental bed of preeclamptic women of African ancestry living with HIV infection.","authors":"Zinhle P Mlambo, Motshedisi Sebitloane, Thajasvarie Naicker","doi":"10.1007/s00418-024-02341-6","DOIUrl":"10.1007/s00418-024-02341-6","url":null,"abstract":"<p><p>Preeclampsia, a severe pregnancy complication linked to defective placentation, poses significant maternal risks and is characterized by dysregulated angiogenic factors, including placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). Women with HIV/AIDS and receiving ART may face an increased susceptibility to preeclampsia development due to immunological and angiogenic imbalance. This study investigates the immunoexpression of these factors in the context of HIV-associated preeclampsia, utilizing morphometric image analysis. The study cohort comprised 180 women, including 60 normotensive and 120 preeclamptic participants, further stratified by HIV status and gestational age (early-onset PE [EOPE] < 34 weeks and late-onset PE [LOPE] ≥ 34 weeks). Placental bed tissues were immunostained with mouse anti-human sFlt-1 and PlGF antibodies, and the results were analyzed using Zeiss Axio-Vision and GraphPad Prism software. sFlt-1 levels showed no significant overall difference between preeclamptic and normotensive women (p = 0.8661), though slightly increased in the preeclamptic myometrium, independent of HIV status. However, sFlt-1 levels were significantly higher in EOPE compared to both normotensive and LOPE groups. PlGF immunostaining also showed no significant overall difference (p = 0.7387) but was notably lower in preeclamptic pregnancies and significantly higher in EOPE compared to LOPE. HIV status did not significantly impact sFlt-1 or PlGF levels, although sFlt-1 was slightly higher in HIV-negative women, while PlGF was marginally higher in HIV-positive women. These findings highlight the complex role of angiogenic factors in preeclampsia pathophysiology and suggest that antiretroviral therapies (ARTs) may contribute to the dysregulation of these factors due to a heightened immune milieu.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"163 1","pages":"8"},"PeriodicalIF":2.1,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695482","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}
Muhammad Aiman Akmal Shahhiran, Mohamad Fairus Abdul Kadir, Nurshamimi Nor Rashid, Puteri Shafinaz Abdul-Rahman, Shatrah Othman
{"title":"Mechanisms of S-phase arrest and mitochondrial dysfunction in complex III by DHODH inhibitors in tumorigenic TNBC cells.","authors":"Muhammad Aiman Akmal Shahhiran, Mohamad Fairus Abdul Kadir, Nurshamimi Nor Rashid, Puteri Shafinaz Abdul-Rahman, Shatrah Othman","doi":"10.1007/s00418-024-02339-0","DOIUrl":"10.1007/s00418-024-02339-0","url":null,"abstract":"<p><p>Dihydroorotate dehydrogenase (DHODH) inhibitors have recently gained increasing research interest owing to their potential for treating breast cancers. We explored their effects in different breast cancer subtypes, focusing on mitochondrial dysfunction. The sensitivity of different subtypes to the inhibitors was investigated with respect to DHODH expression, tumorigenic, and receptor status. Analysis of respiratory complexes, cell cycle, reactive oxygen species (ROS), and cell differentiation were performed. Four cell lines with different receptor status were included, namely MCF-7, MDAMB-231, SKBR-3, and MCF-10A. We showed that MCF-7 and MDAMB-231 cells of the subtypes (ER<sup>+</sup>/PR<sup>+</sup>/HER2<sup>-</sup>) and (ER<sup>-</sup>/PR<sup>-</sup>/HER2<sup>-</sup>), respectively, were responsive to brequinar. Brequinar (BQR) caused cell cycle arrest in the S-phase in sensitive subtypes of breast cells but induced cell differentiation only in poorly differentiated breast cells. All cell subtypes showed increased generation of ROS, both intracellular and mitochondrial ROS with a greater increase seen in mitochondrial ROS in response to DHODH inhibitor, subsequently contributing to mitochondrial dysfunction. BQR also disrupts the function of complex III in ER<sup>+</sup>/PR<sup>+</sup> and triple negative breast cancer (TNBC) subtypes. Collectively, we have found that MDAMB-231 TNBC cell was the most affected by DHODH inhibition in terms of sensitivity, cell cycle arrest, induction of cell differentiation, production of ROS, and mitochondrial complexes disruption. In conclusion, these findings suggest that DHODH inhibitors can potentially become a valuable targeted therapy for TNBC subtype and further consolidates its therapeutic potential as part of the combinatorial therapy against this resilient breast cancer subtype.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"163 1","pages":"3"},"PeriodicalIF":2.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667637","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}
B Pérez-Fernández, V Vázquez-Román, J M Fernández-Santos, I Martín-Lacave
{"title":"Characterization of primary cilia in different epithelial cells of thyroid gland.","authors":"B Pérez-Fernández, V Vázquez-Román, J M Fernández-Santos, I Martín-Lacave","doi":"10.1007/s00418-024-02328-3","DOIUrl":"10.1007/s00418-024-02328-3","url":null,"abstract":"<p><p>The primary cilium (PC) is a biosensor with diverse functions, depending on cellular type. In the thyroid, where it was first described, PCs are located at the apical pole of the follicular epithelium, sensing the lumen's environment. They probably contribute to follicular homeostasis, although their presence in other thyroid epithelial cells remains unclear. Thyroglobulin, stored in the lumen as colloid, is the primary regulator of thyroid-specific gene expression under constant TSH levels. The mechanism by which thyroglobulin signal is transduced remains unresolved. This study investigates the evolution of PCs in different types of thyroid follicles, based on their functional activity, using both normal human thyroids and functional thyroid pathologies as models. It also compares PC morphology between human and rat thyrocytes and explores their presence in other thyroid epithelial components such as C cells and ultimobranchial remnants. Human and Wistar rat thyroid tissues were analyzed using histological, immunohistochemical, immunofluorescence, and electron microscopy techniques. Morphometric analyses quantified PC changes (frequency and length) in various follicular patterns, and statistical analyses were performed. Four types of thyroid follicles were identified: active, hyperactive, hypoactive, and empty follicles. PCs were most abundant and longest in active and significantly reduced in empty follicles. PCs were more prominent in human than in rat thyrocytes, present in both normal and neoplastic C cells, but sporadic in ultimobranchial remnants. PCs vary according to follicular activity and likely act as mechanosensors in thyroid hormone regulation, detecting colloid density and contributing to the regulation of thyroid hormone biosynthesis.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"163 1","pages":"4"},"PeriodicalIF":2.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667471","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}
Arne K Schierz, Giacomo Rößler, Jan Philipp Schneider, Stefan A Tschanz, Christopher Werlein, Danny D Jonigk, Julia Schipke, Christian Mühlfeld
{"title":"Distribution and volume of mitochondria in alveolar epithelial type 1 cells in infant and adult human lungs.","authors":"Arne K Schierz, Giacomo Rößler, Jan Philipp Schneider, Stefan A Tschanz, Christopher Werlein, Danny D Jonigk, Julia Schipke, Christian Mühlfeld","doi":"10.1007/s00418-024-02332-7","DOIUrl":"10.1007/s00418-024-02332-7","url":null,"abstract":"<p><p>Alveolar epithelial type I (AE1) cells with their wide spatial expansion form approximately 95% of the outer surface area of the air-blood barrier inside the lung. Serial block-face scanning electron microscopy (SBF-SEM) investigations led to the hypothesis that AE1 cell mitochondria are preferentially distributed as aggregates in those parts of AE1 cells that are located above connective tissue pillars between capillaries, thus not increasing the thickness of the diffusion distance for oxygen and carbon dioxide. Furthermore, it was hypothesised that postnatal development requires adapting the amount and distribution of mitochondria in AE1 cells. Human lung samples from three infant (26 and 30 days, 6 months) and three adult (20, 39 and 40 years) samples were investigated by light microscopy, transmission electron microscopy and stereology. The volume fraction of mitochondria was similar in infant and adult lungs with a mean value of 6.3%. The ratio between mitochondrial profiles on top of capillaries or above connective tissue pillars was approximately 3:1 in infants and adults. However, regarding the volume of both cytoplasmic compartments, infants showed a higher number of mitochondrial profiles on top of capillaries while adults showed a higher number above connective tissue pillars. Samples of three additional adult lungs were analysed by confocal laser scanning microscopy. Again, mitochondria were not preferentially found as aggregates above connective tissue pillars. In conclusion, AE1 cell mitochondria were not preferentially found as aggregates, showed the same volume density in infants and adults but differed in distribution between the age groups.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"163 1","pages":"7"},"PeriodicalIF":2.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667486","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}
Gamze Altun, Mehmet Emin Önger, Stefano Geuna, Abubaker El Elhaj, Stefania Raimondo, Ömür Gülsüm Deniz, Suleyman Kaplan
{"title":"The amelioration effects of ankaferd blood stopper, platelet gel, and Momordica charantia on peripheral nerve injury in the rats: a stereological and ultrastructural study.","authors":"Gamze Altun, Mehmet Emin Önger, Stefano Geuna, Abubaker El Elhaj, Stefania Raimondo, Ömür Gülsüm Deniz, Suleyman Kaplan","doi":"10.1007/s00418-024-02333-6","DOIUrl":"10.1007/s00418-024-02333-6","url":null,"abstract":"<p><p>Peripheral nerve injuries are commonly encountered in clinical practice. Peripheral nerve injuries most commonly result in serious problems affecting quality of life. The present study is designed to research the possible neuroprotective effects of Ankaferd blood stopper (ABS), platelet-rich plasma (PRP), and Momordica charantia (MC) on regeneration using unbiased stereological techniques. In total, 30 female 8-10 week Sprague Dawley rats were randomly divided into five equal groups; control (CG), the group exposed to sciatic nerve resection (Gap) (CGG), additionally following the surgical process ABS, MC, and PRP were injected into collagen tube (ABSG, MCG, PRPG). Nucleator and fractionator methods were used to estimate the number of myelinated and unmyelinated axons, axon area, and myelin sheath thickness. Also, an electron microscopic evaluation was performed. Regarding the number of myelinated axons, significant increases were found in the ABSG, MCG, and PRPG compared with CG (p < 0.05). The protective effects of ABS, PRP, and MC on peripheral nerve regeneration in experimental models in rats were shown using electrophysiological and stereological assessment parameters.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"163 1","pages":"5"},"PeriodicalIF":2.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667641","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}
Alessandro Miraglia, Laura Giannotti, Francesco De Nuccio, Antonella Sonia Treglia, Michele Maffia, Dario Domenico Lofrumento, Bruno Di Jeso, Giuseppe Nicolardi
{"title":"Anaplastic thyroid carcinoma: vimentin segregates at the invasive front of tumors in a murine xenograft model.","authors":"Alessandro Miraglia, Laura Giannotti, Francesco De Nuccio, Antonella Sonia Treglia, Michele Maffia, Dario Domenico Lofrumento, Bruno Di Jeso, Giuseppe Nicolardi","doi":"10.1007/s00418-024-02329-2","DOIUrl":"10.1007/s00418-024-02329-2","url":null,"abstract":"<p><p>Anaplastic thyroid carcinoma (ATC) ranks among the most lethal human cancers. Increased migratory and invasive capabilities are critical in malignancy and are often secondary to epithelial-mesenchymal transition (EMT). However, it is not clear whether the invasive behavior of ATC is associated with the presence of EMT. In this study, we used a murine xenograft model (4-week-old male BALB/c NU/NU mice) with the human anaplastic cell line, FRO. We adopted an automated, eye-independent method to reconstruct the total/subtotal area of the tumors. To probe EMT, we evaluated the immunostaining of mesenchymal/epithelial markers at the front and center of the tumors. The transplanted cells invariably gave rise to tumor masses that histologically closely replicated patient tumors. The staining with hematoxylin-eosin and immunostaining with cytokeratin 18, an epithelial marker, were similar. However, the immunostaining of cytokeratin 18 versus vimentin, a mesenchymal marker, were strikingly dissimilar, since vimentin showed a staining concentrated at the front, rapidly declining towards the center of the tumor. The overlay, after color conversion, of cytokeratin and vimentin staining showed maximal coincidence at the front, which was rapidly lost towards the center. The results show EMT signs at the front of the ATC, which are probably at the basis of its tremendous invasiveness. Moreover, methodologically, an automated \"eye-independent\" acquisition of the total/subtotal area of the tumors drove the selection of second, high-magnification, automated field acquisition. Future studies may extend these results along the perspective of a personalized diagnostic procedure.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"163 1","pages":"6"},"PeriodicalIF":2.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667537","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}
{"title":"Novel role of curcumin as inhibitor of β-amyloid-induced lamin fragmentation.","authors":"Md Selim Hossain, Md Aminul Haque, Il-Seon Park","doi":"10.1007/s00418-024-02331-8","DOIUrl":"10.1007/s00418-024-02331-8","url":null,"abstract":"<p><p>Oligomer amyloid beta 42 (Aβ) is considered the key pathogenic molecule in Alzheimer disease (AD) and causes specific lamin fragmentation. Curcumin has been recognized for its protective effects against Aβ-induced toxicity in AD, though its underlying mechanism remains unclear. In this study, the inhibitory mechanism of curcumin against Aβ-induced lamin fragmentation and cell death was investigated. Human neuroblastoma cells were used to examine Aβ-induced lamin fragmentation and lamin deformation by immunoblotting and confocal microscopy, while cell viability was measured using MTT and alamarBlue assay. Caspase and cathepsin L activity were assessed by spectrofluorometry, and Aβ aggregation was evaluated by ThT assay. Our results demonstrated that curcumin inhibited Aβ aggregation, reducing intracellular Aβ uptake by 45% compared to Aβ-treated cells. Curcumin also inhibited the Aβ-induced intracellular calcium rise, subsequently leading to a onefold reduction in cathepsin L activity. This reduction in cathepsin L activity by curcumin blocked the Aβ-induced lamin fragmentation. Collectively, these findings suggest that curcumin inhibits Aβ-induced cell death by preventing Aβ entry and lamin cleavage, providing potential new insights for AD treatment.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"163 1","pages":"2"},"PeriodicalIF":2.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619252","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}
Ana Vitoria Ferreira Dos Santos, Renan Gabriel da Silva Ferreira, Fernanda das Chagas Angelo Mendes Tenorio, Carina Scanoni Maia, Valdemiro Amaro da Silva Junior, Romildo de Albuquerque Nogueira, Bruno Mendes Tenorio
{"title":"Complex shape markers can detect alterations in the spatial distribution of cell nuclei in human lung squamous cell carcinoma: a useful tool for automatic analysis?","authors":"Ana Vitoria Ferreira Dos Santos, Renan Gabriel da Silva Ferreira, Fernanda das Chagas Angelo Mendes Tenorio, Carina Scanoni Maia, Valdemiro Amaro da Silva Junior, Romildo de Albuquerque Nogueira, Bruno Mendes Tenorio","doi":"10.1007/s00418-024-02336-3","DOIUrl":"https://doi.org/10.1007/s00418-024-02336-3","url":null,"abstract":"<p><p>Lung cancer is the leading cause of cancer-related death. The use of computational methods to quantify changes that are not perceptible to the human eye is increasing in digital pathology imaging and has quickly improved detection rates at a low cost. Therefore, the present study aims to use complex computational shape markers as tools for automated analysis of the spatial distribution of cells in microscopy images of squamous cell lung carcinoma (SqCC). Photomicrographs from pathology glass slides in the LC25000 dataset were used in this study. Compared with those of the control, the fractal dimension (28%) and lacunarity (41%) of the cell nuclei changed in SqCC. The multifractal analysis revealed a significant difference in parameters Dq, α, and f(α) for all values of q (-10 to + 10), with a greater increase for more positive q values. The values at q + 10 increased by 34% for Dq, 36% for α, and 53% for f(α) in the SqCC images. The circularity, area, and perimeter also changed in the SqCC images. However, the parameters of aspect ratio, roundness, and solidity did not significantly differ between SqCC and benign tissue. The complex shape markers with the greatest changes in this study were the f(α) values for multifractality (53%) and lacunarity (41%). In conclusion, automated quantification of the spatial distribution of cell nuclei can be a fast, low-cost tool for evaluating the microscopic characteristics of SqCC; therefore, complex shape markers could be useful tools for software and artificial intelligence to detect lung carcinoma.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"163 1","pages":"1"},"PeriodicalIF":2.1,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582730","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}
{"title":"Effects of ∆-9 tetrahydrocannabinol on the small intestine altered by high fructose diet: A Histopathological study.","authors":"Basak Isildar, Alisa Bahar Beydogan, Ece Koyuturk, Zeynep Mine Coskun Yazici, Meral Koyuturk, Sema Bolkent","doi":"10.1007/s00418-024-02311-y","DOIUrl":"10.1007/s00418-024-02311-y","url":null,"abstract":"<p><p>The consumption of fructose is increasing day by day. Understanding the impact of increasing fructose consumption on the small intestine is crucial since the small intestine processes fructose into glucose. ∆9-Tetrahydrocannabinol (THC), a key cannabinoid, interacts with CB1 and CB2 receptors in the gastrointestinal tract, potentially mitigating inflammation. Therefore, this study aimed to investigate the effects of the high-fructose diet (HFD) on the jejunum of rats and the role of THC consumption in reversing these effects. Experiments were conducted on Sprague-Dawley rats, with the experimental groups as follows: control (C), HFD, THC, and HFD + THC. The HFD group received a 10% fructose solution in drinking water for 12 weeks. THC groups were administered 1.5 mg/kg/day of THC intraperitoneally for the last four weeks. Following sacrification, the jejunum was evaluated for mucus secretion capacity. IL-6, JNK, CB2 and PCNA expressions were assessed through immunohistochemical analysis and the ultrastructural alterations via transmission electron microscopy. The results showed that fructose consumption did not cause weight gain but triggered inflammation in the jejunum, disrupted the cell proliferation balance, and increased mucus secretion in rats. Conversely, THC treatment displayed suppressed inflammation and improved cell proliferation balance caused by HFD. Ultrastructural examinations showed that the zonula occludens structures deteriorated in the HFD group, along with desmosome shrinkage. Mitochondria were found to be increased due to THC application following HFD. In conclusion, the findings of this research reveal the therapeutic potential of THC in reversing HFD-related alterations and provide valuable insights for clinical application.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":" ","pages":"363-372"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897326","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":"HOXC10 promotes hypertrophic scar fibroblast fibrosis through the regulation of STMN2 and the TGF-β/Smad signaling pathway.","authors":"Xin Zhou, Song Lin","doi":"10.1007/s00418-024-02317-6","DOIUrl":"10.1007/s00418-024-02317-6","url":null,"abstract":"<p><p>The pathophysiology of hypertrophic scar (HS) shares similarities with cancer. HOXC10, a gene significantly involved in cancer development, exhibits higher expression levels in HS than in normal skin (NS), suggesting its potential role in HS regulation. And the precise functions and mechanisms by which HOXC10 influences HS require further clarification. Gene and protein expressions were analyzed using raeal-time quantitative polymerase chain reaction (RT-qPCR) and western blot techniques. Cell proliferation and migration were evaluated using EdU proliferation assays, CCK-8 assays, scratch assays, and Transwell assays. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were conducted to investigate the interactions between HOXC10 and STMN2. HOXC10 and STMN2 expression levels were significantly higher in HS tissues compared with NS tissues. Silencing HOXC10 led to decreased activation, proliferation, migration, and fibrosis in hypertrophic scar fibroblasts (HSFs). Our findings also indicate that HOXC10 directly targets STMN2. The promotional effects of HOXC10 knockdown on HSF activation, proliferation, migration, and fibrosis were reversed by STMN2 overexpression. We further demonstrated that HOXC10 regulates HSF activity through the TGF-β/Smad signaling pathway. HOXC10 induces the activation and fibrosis of HSFs by promoting the transcriptional activation of STMN2 and engaging the TGF-β/Smad signaling pathway. This study suggests that HOXC10 could be a promising target for developing treatments for HS.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":" ","pages":"403-413"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995687","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}