Histology and histopathology Vol.38, nº3 (2023)
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- PublicationOpen AccessShort-term high fat feeding induces inflammatory responses of tuft cells and mucosal barrier cells in the murine stomach(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Widmayer, Patricia; Pregitzer, Pablo; Breer, HeinzFeeding mice with a high fat diet (HFD) induces inflammation and results in changes of gene expression and cellular composition in various tissues throughout the body, including the gastrointestinal tract. In the stomach, tuft cells expressing the receptor GPR120 are capable of sensing saturated long chain fatty acids (LCFAs) and thus may be involved in initiating mechanisms of mucosal inflammation. In this study, we assessed which cell types may additionally be affected by high fat feeding and which candidate molecular mediators might contribute to mucosaprotective immune responses. A high fat dietary intervention for 3 weeks caused an expansion of tuft cells that was accompanied by a higher frequency of mucosal mast cells and surface mucous cells which are a known source of the insult-associated cytokine interleukin 33 (IL-33). Our data demonstrate that both brush and mucosal mast cells comprise the enzyme ALOX5 and its activating protein FLAP and thus have the capacity for synthesizing leukotriene (LT). In HFD mice, several tuft cells showed a perinuclear colocalization of ALOX5 with FLAP which is indicative of an active LT synthesis. Monitoring changes in the expression of genes encoding elements of LT synthesis and signaling revealed that transcript levels of the leukotriene C4 synthase, LTC4S, catalyzing the first step in the biosynthesis of cysteinyl (cys) LTs, and the cysLT receptors, cysLTR2 and cysLTR3, were upregulated in mice on HFD. These mice also showed an increased expression level of IL-33 receptors, the membranebound ST2L and soluble isoform sST2, as well as the mast cell-specific protease MCPT1. Based on these findings it is conceivable that upon sensing saturated LCFAs tuft cells may elicit inflammatory responses which result in the production of cysLTs and activation of surface mucous cells as well as mucosal mast cells regulating gastric mucosal function and integrity.
- PublicationOpen AccessExpression of Foxp3 and TLR4 in human papillary thyroid carcinoma and its clinical significance(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Xin, Jingwei; Fu, Haiying; Zhang, Jiaping; Zou, Hongrui; Li, Qi; Yang, Wei; Sun, HuiThis study aimed to explore the association of Foxp3 and TLR4 with clinical pathological characteristics in papillary thyroid carcinoma (PTC) patients. Methods 78 cases of PTC were used as experimental group and 20 cases of normal thyroid tissue were used as control group. The expression of Foxp3 and TLR4 in thyroid tissue from the two groups was detected by immunohistochemistry, and the experimental group was divided into several groups on the basis of different clinicopathological indicators. The association between Foxp3 and TLR4 expression and clinicopathological parameters was statistically analyzed. Results Foxp3 and TLR4 were expressed in higher levels in PTC than in normal thyroid tissue (P<0.05). Foxp3 was mainly localized in the cytoplasm and nucleus of PTC cells, while TLR4 was found in the cytoplasm and cell membrane of cancer cells. The expression of both proteins associated with lymph node metastasis and TNM clinical stage (P<0.05). The expression of Foxp3 correlated with the expression of TLR4 in tested PTC tissues (P<0.05). In addition, the result of confocal fluorescence microscopy showed that Foxp3 and TLR4 co-localized in PTC cells. Conclusion Foxp3 and TLR4 were upregulated and associated with lymph node metastasis and advanced TNM stage in PTC tissues. Together they may act as valuable factors for the identification of high-risk PTC patients.
- PublicationOpen AccessCirc_0031242 regulates the functional properties of hepatocellular carcinoma cells through the miR-944/MAD2L1 axis(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Lin, Jianwei; Lin, Zenghai; Hua, Yaqiong; Chen, YanBackground. Circular RNAs (circRNAs) possess key functions in the pathogenesis of hepatocellular carcinoma (HCC). Nonetheless, the actions of individual circRNAs in HCC remain undefined. Methods. circ_0031242, miR-944, and MAD2L1 expression were quantified by qRT-PCR. Transwell assay was utilized to examine cell invasion and migration. Glucose consumption and lactate production were measured to assess the impact on glycolysis. The relationships among circ_0031242, MAD2L1, and miR944 were examined via luciferase reporter assay. Results. circ_0031242 was notably augmented in HCC. Loss of function of circ_0031242 hindered cell proliferation, invasion, migration, glycolysis, and promoted apoptosis, as well as impeding HCC tumor growth. circ_0031242 directly targeted miR-944. Inhibition of miR-944 counteracted the effects of sicirc_0031242 on HCC cells. Additionally, miR-944 was proved to directly target MAD2L1 in HCC cells. Moreover, the promotion of MAD2L1 was able to rescue the inhibition of high miR-944 expression on HCC cell progression. Meanwhile, circ_0031242 involved the post-transcriptional modulation of MAD2L1 through miR-944. Conclusion. This study suggested that circ_0031242 regulated tumor cell progression and tumor growth through the miR-944/MAD2L1 axis in HCC.
- PublicationOpen AccessHistopathogenesis of bone- and soft-tissue tumor spectrum with USP6 gene rearrangement: multiple partners involved in the tissue repair process.(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Legrand, Mélanie; Jourdan, Marie Lise; Pinieux, Gonzague dePrimary aneurysmal bone cyst, nodular fasciitis, myositis ossificans and related lesions as well as fibroma of tendon sheath are benign tumors that share common histological features and a chromosomal rearrangement involving the ubiquitin-specific peptidase 6 (USP6) gene. The tumorigenesis of this tumor spectrum has become complex with the identification of an increasing number of new partners involved in USP6 rearrangements. Because traumatic involvement has long been mentioned in the histogenesis of most lesions in the USP6 spectrum and they morphologically resemble granulation tissue or callus, we attempted to shed light on the function and role USP6 partners play in tissue remodelling and the repair process and, to a lesser extent, bone metabolism
- PublicationOpen AccessACE2 in male genitourinary and endocrine systems: Does COVID-19 really affect these systems?(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Xu, Chen Shuo; Yang, Wan XiThe virus that causes COVID-19 (Corona Virus Disease 2019), SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), is causing a worldwide pandemic, posing a substantial threat to human health. Patients show signs of pneumonia, ARDS, shock, acute cardiac injury, acute kidney injury and other complications. The SARS-CoV-2 receptor is angiotensin converting enzyme 2 (ACE2), which is an important component of the renin-angiotensin system (RAS). In addition, TMPRSS2 or other cofactors are needed to allow the virus to enter the host. Clinical patients have exhibited varying degrees of genitourinary and endocrine system damage, and some studies have also reported potential risks to the genitourinary and endocrine systems. This article reviews the mechanism underlying SARS-CoV-2 infection and the current studies on the male genitourinary and endocrine systems and proposes that more attention should be directed towards human reproductive and endocrine health during the SARS-CoV-2 epidemic.
- PublicationOpen AccessCircular RNA circ_SKA3 enhances gastric cancer development by targeting miR-520h(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Wang, Chuntao; Jiang, Hao; Peng, Jiaqun; Weng, Duanshun; Zhang, Yu; Zhou, Yanxun; Zhang, QinPurpose. To explore the mechanisms of action of circ_SKA3 in gastric cancer (GC), which are still not fully understood. Methods. Subcellular localization assay was used to analyze the localization of circ_SKA3, and Actinomycin D assay was applied to confirm the stability of circ_SKA3. The levels of circ_SKA3, microRNA (miR)- 520h, and cell division cycle 42 (CDC42) mRNA were gauged by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of CDC42 and proliferating cell nuclear antigen (PCNA) were assessed by western blot. Cell proliferation, colony formation, cell cycle distribution, apoptosis, migration, and invasion were detected by 3-[4,5-dimethylthiazol-2-yl]- 2, 5-diphenyltetrazolium bromide (MTT), 5-Ethynyl-2’- Deoxyuridine (EdU) incorporation, colony formation, flow cytometry, and transwell assays, respectively. Directed relationship between miR-520h and circ_SKA3 or CDC42 was verified by a dual-luciferase reporter assay. Mouse xenograft experiments were used to elucidate the impact of circ_SKA3 in vivo. Results. Overexpression of circ_SKA3 was validated in GC tissues and cells. The down-regulation of circ_SKA3 suppressed proliferation, cell cycle progression, colony formation, migration, invasion, and promoted cell apoptosis in vitro, as well as weakening tumor growth in vivo. Circ_SKA3 directly bound to miR-520h, and circ_SKA3 regulated CDC42 expression through miR-520h. Circ_SKA3 exerted regulatory effects on GC cell behaviors by inhibiting miR-520h. Furthermore, CDC42 was a functional target of miR520h in regulating GC cell behaviors. Conclusion. Our findings established a strong molecular mechanism, the miR-520h/CDC42 axis, at least in part, for the oncogenic role of circ_SKA3 in GC.
- PublicationOpen AccessThe CCL27-CCR10 axis contributes to promoting proliferation, migration, and invasion of lung squamous cell carcinoma(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Li, Baijun; Wei, Caizhou; Zhong, Yonglong; Huang, Jianwei; Li, RizhuLung cancer is characterized by its high mortality and morbidity. A deep understanding of the molecular mechanisms of lung cancer tumorigenesis helps to develop novel lung cancer diagnostic and therapeutic strategies. However, the picture of the associated molecular landscape is not yet complete. As understood, chemokine-receptor interactions contribute much to lung cancer tumorigenesis, in which CCR10 also plays an important role. This study aimed to expand the knowledge of CCR10 in lung squamous cell carcinoma (LUSC) in the manner of molecular mechanism and biological functions. Using GEPIA database, the survival analysis between LUSC patients with high and low CCR10 expressions was performed, showing that CCR10 could be regarded as a risk factor for LUSC patients. Subsequently, CCR10 protein and mRNA expressions in LUSC were examined by qRTPCR and western blot respectively. The results indicated that CCR10 was highly expressed in LUSC cells. The results of CCK-8, colony formation, and Transwell assays presented that CCL27, the ligand of CCR10, promoted proliferative, migratory, and invasive abilities of LUSC cells by activating CCR10. Also, the PI3K/AKT signaling pathway was verified as the involved pathway by western blot. Overall, it could be concluded that the CCL27-CCR10 regulatory axis can activate the PI3K/AKT pathway fostering the malignant features of LUSC cells.
- PublicationOpen AccessUp-regulation of CMKLR1 in endometriosis and its relationship with inflammatory responses(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Zhang, Zhe; Ding, Yumei; Li, Junjie; Su, ShanInflammation plays a critical role in the pathogenesis of endometriosis. We aimed to study the proinflammatory effect of Chemerin chemokine-like receptor 1 (CMKLR1) in patients with endometriosis. Sixty patients with endometriosis and 50 healthy controls were recruited in this study for the collection of endometrial samples and peritoneal fluid. The expression levels of CMKLR1, IL-6, MCP-1, and TNFα in peritoneal fluid and endometrial tissues were detected by ELISA, qRT-PCR, and immunohistochemical staining. Human endometrial stromal cells (HESCs) were used to measure the Chemerin-induced CMKLR1 activation and inflammatory responses. CMKLR1 level was significantly up-regulated in peritoneal fluid and endometrial tissues in patients with endometriosis. Interestingly, CMKLR1 overexpression positively correlated with pro-inflammatory cytokines and chemokine in both peritoneal fluid and ectopic endometrium. Chemerin treatment increased the expression of CMKLR1, and aggravated inflammatory responses in HESCs. CMKLR1 is up-regulated in peritoneal fluid and endometrial tissues, and promotes the inflammatory responses in of endometriosis.
- PublicationOpen AccessThe circCDK17/miR-122-5p/ASF1B axis regulates the progression of cervical cancer(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Qiu, Fang; Ou, Dafen; Tan, Hanxing; Gao, Yan; Z, DanBackground. Cervical cancer (CC) ranks fourth in terms of incidence and fourth in mortality overall in women worldwide. Circular RNAs (circRNAs) have been shown to be involved in the development of CC. However, the function of circRNA cyclin dependent kinase 17 (circCDK17, hsa_circ_ 0002762) in CC pathogenesis has not been studied. Methods. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of related genes. MTT, thymidine analog 5-ethynyl-2’- deoxyuridine (EdU), flow cytometry, transwell and wound-healing assays were designed to analyze cell proliferation, cell cycle progression, migration and invasion, respectively. Western blot was utilized to examine the protein levels of Cyclin D1, E-cadherin and Vimentin. The relationship between miR-122-5p and circCDK17 or ASF1B was verified by dual-luciferase reporter assay. The xenograft model was established to study the role of circCDK17 in vivo. Results. CircCDK17 and anti-silencing function 1B histone chaperone (ASF1B) were highly expressed in CC tissues and cells. Silencing circCDK17 reduced the proliferation, migration and invasion of CC cells. MiR122-5p was a target of circCDK17. Silencing circCDK17 inhibited the malignant behaviors of CC cells by releasing miR-122-5p. Moreover, ASF1B was a target of miR-122-5p. Overexpression of ASF1B partially restored the inhibitory effects of circCDK17 silencing on cell proliferation, migration and invasion. Animal experiments confirmed the anti-tumor effect of circCDK17 knockdown in vivo. Conclusion. Our study demonstrates that circCDK17 regulates the expression of ASF1B by miR-122-5p competition and thus promotes the development of CC, providing a novel targeted therapy for CC.
- PublicationOpen AccessElucidating the role of PRMTs in prostate cancer using open access databases and a patient cohort dataset(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Grypari, Ioanna Maria; Pappa, Ioanna; Papastergiou, Thomas; Zolota, Vassiliki; Bravou, Vasiliki; Melachrinou, Maria; Megalooikonomou, Vasileios; Tzelepi, VasilikiProtein arginine methylation is an understudied epigenetic mechanism catalyzed by enzymes known as Protein Methyltransferases of Arginine (PRMTs), while the opposite reaction is performed by Jumonji domain- containing protein 6 (JMJD6). There is increasing evidence that PRMTs are deregulated in prostate cancer (PCa). In this study, the expression of two PRMT members, PRMT2 and PRMT7 as well as JMJD6, a demethylase, was analyzed in PCa. Initially, we retrieved data from The Cancer Genome Atlas (TCGA) project and the Gene Expression Omnibus (GEO) database to explore the differential expression of various PRMT family members in patients with PCa and then applied immunohistochemistry in a patient cohort across the spectrum of PCa, including non-neoplastic prostate tissue and lymph node metastatic foci. The results from the TCGA analysis revealed that PRMT7, PRMT6 and PRMT3 expression increased while PRMT2, PRMT9 and JMJD6 levels decreased in the tumor compared to non-neoplastic prostate. Results from the GEO datasets were similar, albeit not identical with the TCGA results, with PRMT7 and PRMT3 being upregulated and PRMT2 and JMJD6 being downregulated in the tumor compared to non-neoplastic tissue in some of them. In addition, PRMT7 levels decreased with stage and grade progression in the TCGA analysis. In the patient cohort, both PRMTs and JMJD6 were overexpressed in PCa compared to non-neoplastic tissue, and nuclear PRMT2 and JMJD6 were upregulated in lymph node metastasis, too. PRMT7 and JMJD6 expression were upregulated with the progression of stage and JMJD6 was also increased with the elevation of grade. After androgen ablation therapy, nuclear expression of PRMT7 and JMJD6 were elevated compared to untreated tumors. PRMT2, PRMT7 and JMD6 were also correlated with markers of EMT and cell cycle regulators. Finally, our findings indicate that PRMTs and JMJD6 are involved in prostate cancer progression and revealed a potential interplay of PRMTs with EMT mediators, underscoring the need for therapeutic targeting of arginine methylation in prostate cancer.