Wei He, De-Long Meng, Dan Yang, Qing-You Chen, Li Li, Li-Hua Wang
{"title":"miRNA-192-5p targets Dyrk1a to attenuate cerebral injury in MCAO mice by suppressing neuronal apoptosis and neuroinflammation.","authors":"Wei He, De-Long Meng, Dan Yang, Qing-You Chen, Li Li, Li-Hua Wang","doi":"10.5603/fhc.96703","DOIUrl":"10.5603/fhc.96703","url":null,"abstract":"<p><strong>Introduction: </strong>Ischemic stroke (IS) is a leading cause of disability and mortality worldwide. Several studies have demonstrated the involvement of microRNAs (miRNAs) in brain diseases. miRNA-192-5p is a regulatory molecule in neurodegenerative diseases and its expression was found to be significantly downregulated in the whole blood samples of IS patients, but the specific role of miRNA-192-5p in IS not fully understood. Here, we investigated the role of miRNA-192-5p in a murine model of acute cerebral injury after IS.</p><p><strong>Material and methods: </strong>Male C57BL/6J mice received an intracerebroventricular (i.c.v.) injection of agomir-192-5p or antagomir-192-5p 2 h before middle cerebral artery occlusion (MCAO). Infarct volume was assessed by 2,3,5 triphenyltetrazolium chloride (TTC) staining. Brain slices were subjected to Fluoro-Jade B, TUNEL, and immunofluorescence stainings. Contents of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) were measured using enzyme-linked immunosorbent assay (ELISA) kits. In vitro, murine microglial BV-2 cells were subjected to oxygen-glucose deprivation (OGD), and the contents of pro-inflammatory cytokines were measured in cell lysates.</p><p><strong>Results: </strong>miRNA-192-5p was downregulated in the ischemic penumbra of the cerebral cortex. Pretreatment with agomir-192-5p attenuated neurological deficits and reduced cerebral edema and infarct volume in MCAO mice. Agomir-192-5p-treated animals had fewer degenerating and apoptotic neurons in the ischemic penumbra. Additionally, agomir-192-5p significantly suppressed neuroinflammation as evidenced by decreased immunostaining for GFAP and Iba1 and decreased levels of pro-inflammatory cytokines. Antagomir-192-5p pretreatment showed the opposite effect. Furthermore, dual specificity tyrosine phosphorylation regulated kinase 1A (Dyrk1a) was identified as a target gene of miRNA-192-5p, and the elevated Dyrk1a expression in the ischemic penumbra was markedly reduced by agomir-192-5p. Dyrk1a overexpression in BV-2 microglial cells impaired miRNA-192-5p-mediated inhibition of OGD-induced activation of BV-2 microglial cells. Opposite results were obtained using miRNA-192-5p inhibitor and Dyrk1a siRNA.</p><p><strong>Conclusions: </strong>We found that intracerebroventricular administration of miRNA-192-5p before MCAO attenuatedacute cerebral injury by suppressing neuronal apoptosis and neuroinflammation in mice, and these protective effects might be mediated by downregulation of Dyrk1a. This study would help identify novel therapeutic targets for IS.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":"61 4","pages":"217-230"},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139520208","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":"Curcumin exerts protective effects on the thyroid gland in propylthiouracil-treated rats.","authors":"Monika A Papież","doi":"10.5603/fhc.96497","DOIUrl":"10.5603/fhc.96497","url":null,"abstract":"<p><strong>Introduction: </strong>Among the plant ingredients, some compounds interfere with the functions of the thyroid gland. However, there is limited research on the effect of curcumin (CMN) on the functions of this gland. The aim of this study was to analyze the effect of CMN on morphology, histochemical reactivity of cytochrome c oxidase (CCO) and secretion functions of the thyroid gland under conditions of hypothyroidism induced by propylthiouracil (PTU).</p><p><strong>Material and methods: </strong>The rats were treated for 30 days by gavage with CMN (100 mg/kg b.w.) and/or PTU (1 mg/kg b.w.). Control rats received vehicle only. Histomorphometric tests were performed on the thyroid glands, cytochrome c oxidase activity was visualized using the histochemical method, and the levels of thyroid hormones were measured using the radioimmunoassay method.</p><p><strong>Results: </strong>Rats receiving PTU showed compensatory changes in their thyroid glands, including a significant increase in thyroid epithelium height, a decrease in colloid volumen density, a decrease in the percentage of small follicles, an increase in medium-sized follicles compared to the control group, as well as a significant increase in CCO histochemical reactivity in the columnar epithelium and a decrease in FT4 serum level compared to the control group. The administration of CMN reversed these adverse changes caused by PTU. The PTU + CMN group exhibited a significant decrease in the height of the thyroid follicle epithelium compared to the PTU group. The percentage of small and medium-size follicles in the CMN + PTU group did not differ from the control group. Furthermore, CCO reactivity in the cubic epithelium and serum FT4 levels increased compared to the PTU group. Administration of CMN alone resulted in a significant increase in FT4 levels compared to the control group.</p><p><strong>Conclusions: </strong>The administration of CMN to rats with induced hypothyroidism resulted in a reduction of hyperplasia, hypertrophy, and increase in secretory activity of the thyroid gland. These findings suggest the protective effect of CMN against induced hypothyroidism.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":"143-152"},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10657906","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}
Weixing Mo, Qingqing Yu, Xiufeng Kuang, Ting He, Jun Lou, Rongjun Tang, Ke Zhang, Lingdi Li, Linfang Zhao
{"title":"Focused ultrasound restrains the growth of orthotopic colon cancer via promoting pyroptosis.","authors":"Weixing Mo, Qingqing Yu, Xiufeng Kuang, Ting He, Jun Lou, Rongjun Tang, Ke Zhang, Lingdi Li, Linfang Zhao","doi":"10.5603/FHC.a2023.0003","DOIUrl":"https://doi.org/10.5603/FHC.a2023.0003","url":null,"abstract":"<p><strong>Introduction: </strong>Focused ultrasound (FUS) is a non-invasive tumor therapy technology emerging in recent years, which can treat various solid tumors. However, it is unclear whether FUS can affect the pyroptosis of colon cancer (CC) cells. Here, we analyzed the effect of FUS on pyroptosis in the orthotopic CC model.</p><p><strong>Material and methods: </strong>After an orthotopic CC mouse model was constructed by injecting CT26-Luc cells, BABL/C mice were allocated to the normal, tumor, FUS, and FUS + BAY11-7082 (pyroptosis inhibitor) groups. We monitored the tumor status of the mice through in vivo fluorescence image analysis. The histopathological injury of the intestinal tissue and the expression of IL-1β, IL-18, caspase-recruitment domain (ASC), cleaved caspase-1, gasdermin D (GSDMD), and NLRP3 of the CC tumors were examined utilizing hematoxylin and eosin staining, immunohistochemical assay, and Western blot.</p><p><strong>Results: </strong>FUS restrained the fluorescence intensity of the tumors in orthotopic CC mice, while FUS-mediated suppression of the bioluminescent signal of the tumors was alleviated by BAY11-7082. FUS was found to relieve the injury of the intestinal tissues in CC mice as revealed by morphology. Furthermore, the expressions of IL-1β, IL-18, GSDMD, ASC, cleaved caspase-1, and NLRP3 of the CC tumors in the FUS group were higher than those in the tumor group, while BAY11-7082 addition partly reversed the FUS's effects on orthotopic CC model mice.</p><p><strong>Conclusions: </strong>Our results pointed out that FUS presented anti-tumor activity in experimental CC, and its mechanism was correlated with the promotion of pyroptosis.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":"61 1","pages":"47-55"},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9201844","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":"Expression of HIF1α, BNIP3, and beclin-1 in the brain of newborn and adult yaks (Bos grunniens).","authors":"Qian Zhang, Yan Cui, Sijiu Yu, Junfeng He, Yangyang Pan, Meng Wang, Gengquan Xu","doi":"10.5603/FHC.a2023.0005","DOIUrl":"https://doi.org/10.5603/FHC.a2023.0005","url":null,"abstract":"<p><strong>Introduction: </strong>As a main consumer of energy, the brain is particularly susceptible to the effects of hypoxia. However, during long-term evolution, the brain of the plateau yak developed adaptive mechanisms enabling it to maintain normal physiological conditions.</p><p><strong>Material and methods: </strong>A total of 20 male yaks belonging to two age groups [newborns (1-6 days old; n = 10) and adults (3-5 years old; n = 10)] were obtained, and the brain tissue was fixed and processed by standard methods. RT-qPCR, ELISA and IHC assays were used to investigate the expression and localization of HIF1α, BNIP3 and beclin-1 in the hippocampus, cerebral cortex, thalamus, medulla oblongata and cerebellum of newborn and adult yak brains and to explore their potential neuroprotective role.</p><p><strong>Results: </strong>We found that the expression levels of HIF1α, BNIP3 and beclin-1 at the mRNA and protein levels varied in the different regions of yak brain, with the highest expression observed in the hippocampus, followed by the cerebral cortex, thalamus, medulla oblongata and the cerebellum. Moreover, the HIF1α, BNIP3 and beclin-1 expression were significantly higher in the newborn yaks' brains than in the adult yak. The IHC results showed that HIF1α, BNIP3 and beclin-1 were mainly distributed in the neurons of the cerebral cortex, hippocampus, thalamus, medulla oblongata and cerebellum. In particular, HIF1α accumulated in the nucleus and cytoplasm. Furthermore, the immunoreactivity of BNIP3 and beclin-1 was concentrated in the cytoplasm.</p><p><strong>Conclusions: </strong>The results indicate that the yak hippocampus and cerebral cortex may be more resistant to hypoxia than thalamus, medulla oblongata and cerebellum, and the expression of BNIP3 and beclin-1 may be regulated by HIF1α to serve a neuroprotective role in the yak's brain to adaptation to hypoxia. Additionally, the brain of adult yaks may have a higher tolerance to hypoxia than the brain of newborn yaks.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":"61 1","pages":"26-33"},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9257851","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":"The effectiveness of using dye models for small tissue biopsies in the surgical pathology laboratory.","authors":"Predaporn Nonsiri, Potchara Srivilai, Supatsorn Onkaew, Nontawat Benjakul","doi":"10.5603/FHC.a2023.0008","DOIUrl":"https://doi.org/10.5603/FHC.a2023.0008","url":null,"abstract":"<p><strong>Introduction: </strong>Losing of small tissues during tissue preparatory steps may seriously affect pathological diagnostic performance. Using an appropriate tissue marking dye could be an alternative solution. Therefore, the aim of the study was to find a suitable tissue marking dye to enhance the observable ability of various types of small-size tissues during several steps of tissue preparation.</p><p><strong>Material and methods: </strong>Various small-size samples of various organs and tissues (0.2 to 0.3 cm), including breast, endometrial, and cervical tissue, stomach, small and large intestine, lung, and kidney, were marked with different dyes such as merbromin, hematoxylin, eosin, crystal violet, and alcian blue prior to tissue processing step and their colored-observable ability was evaluated by pathology assistants. Moreover, the diagnostic interfering effect of each tissue marking dye was determined by pathologists.</p><p><strong>Results: </strong>Merbromin, hematoxylin, and alcian blue increased the colored-observable ability of small tissue samples. We suggest using hematoxylin as a tissue marking dye over merbromin and alcian blue because of less toxicity and no interference effect in the step of routine pathological slide examination.</p><p><strong>Conclusions: </strong>Hematoxylin could be a suitable tissue marking dye for small-size samples and may improve the preanalytical process of tissue preparation in pathological laboratories.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":"61 2","pages":"123-129"},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10173168","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":"Inhibition of heat shock protein 47 suppressed collagen production in Tenon's capsule fibroblasts.","authors":"Weiwei Wang, Haiyan lI","doi":"10.5603/fhc.96514","DOIUrl":"10.5603/fhc.96514","url":null,"abstract":"<p><strong>Introduction: </strong>Glaucoma is the leading cause of irreversible blindness worldwide, and conjunctival bleb scarring remains the most frequent reason for the failure of glaucoma filtration surgery. Excessive proliferation of fibroblasts from Tenon's capsule and excessive deposition of collagen contribute to the scarification of the conjunctival bleb. Heat shock protein 47 (HSP47) is assumed to act as a collagen-specific molecular chaperone, and thereby involved in the pathogenesis of fibrotic diseases. Therefore, we investigated the effect of HSP47 knockout against collagen type I (COLI) production in rat tenon's fibroblasts.</p><p><strong>Material and methods: </strong>Newborn rat tenon's fibroblasts were cultured and verified by anti-vimentin antibody. Transfection efficiency of small interference RNA targeted against HSP47 was confirmed by quantitative real-time polymerase chain reaction (RT-qPCR) at 48 h after siRNA transfection and by western blot at 72 h after transfection. The mRNA and protein expression of HSP 47 and COLI were detected by RT-qPCR and western blot. The proliferation of cells was measured by cell counting kit-8 assay.</p><p><strong>Results: </strong>HSP47 siRNA down-regulated the mRNA and protein levels of HSP47 in rat Tenon's fibroblasts, and suppressed the mRNA and protein expression of COLI. Moreover, HSP47 siRNA had no significant effect on proliferation of rat Tenon's fibroblasts.</p><p><strong>Conclusions: </strong>HSP47 siRNA inhibits the production of COLI in rat Tenon's fibroblasts, and may be the potential therapeutic method in bleb scarring after glaucoma filtration surgery.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":"153-159"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10363178","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":"Expression of CD105 but not of E-cadherin is associated with malignancy recurrence and disease-free interval in laryngeal cancer in men.","authors":"Elvir Zvrko, Ljiljana Vuckovic","doi":"10.5603/fhc.97035","DOIUrl":"10.5603/fhc.97035","url":null,"abstract":"<p><strong>Introduction: </strong>In this study we analyzed CD105 (endoglin) and E-cadherin expression in laryngeal squamous cell carcinoma (LSCC) to evaluate their clinicopathologic significance.</p><p><strong>Material and methods: </strong>Expression of CD105 and E-cadherin was examined immunohistochemically using paraffin-embedded archival tissues of 72 (35 glottic and 37 supraglottic) previously untreated LSCC male patients. The mean value of the positively-stained microvessels for CD105 counted in four hot spots for each case was used as the final intratumoralmicrovessel density (MVD). A staining score of E-cadherin was calculated based on the percentage of cells stained (0-100%).</p><p><strong>Results: </strong>MVD was significantly higher in patients with advanced TNM stage (P = 0.004) and younger than 65 (P = 0.008). Nodal metastases were more frequent in the cases with low E-cadherin expression (P = 0.000). Tumor recurrence was associated with advanced TNM stage (P = 0.035) and high MVD (P = 0.002). A high MVD was an independent predictor of malignancy recurrence (P = 0.021). The log-rank test showed a significant difference in the disease-free interval in patients stratified according to the MVD value (P = 0.016). Spearman's rank correlation test did not show a significant correlation between E-cadherin and CD105 expression.</p><p><strong>Conclusions: </strong>CD105-assessed MVD and expression of E-cadherin are promising prognostic factors for the outcome of patients with LSCC. Increased expression of CD105 could help predict patients with an increased risk of developing loco-regional recurrence after surgical treatment. Decreased E-cadherin expression is a potential predictor of lymph node metastases.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":"183-192"},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41125366","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":"Correlation between stromal Th and Tc lymphocytes and PD-L1 expression in early breast cancer tumors.","authors":"Jelena Vučinić, Ljiljana Vučković, Janja Raonić","doi":"10.5603/fhc.97855","DOIUrl":"10.5603/fhc.97855","url":null,"abstract":"<p><strong>Introduction: </strong>Prognostic and predictive value of PD-L1 as a biomarker in breast cancer remains controversial. While some studies suggest its association with negative prognostic parameters, others reported a highly significant association between PD-L1 expression and tumor-infiltrating lymphocytes, which are known to be an independent favorable prognostic factor. The aim of present study is to examine the relationship between immune response markers and PD-L1 expression in early breast cancer.</p><p><strong>Material and methods: </strong>Immunohistochemical expression of PD-L1, along with density and composition of stromal lymphocytic infiltrate and peritumoral lymphoid aggregates was analyzed in 95 samples of invasive breast cancer.</p><p><strong>Results: </strong>A strong positive correlation between PD-L1 expression and the density of stromal lymphocytic infiltrate and peritumoral lymphoid aggregates was identified and a cut-off value of 53% coverage of tumor stroma by lymphocytes, with which PD-L1 positivity can be predicted with excellent diagnostic accuracy, was determined for the first time using statistical methods. Additionally, PD-L1 positivity was observed significantly more often in tumors with higher absolute number of both CD4 and CD8 T-lymphocytes in the stromal infiltrate. No significant correlation with molecular subtype of breast cancer was found.</p><p><strong>Conclusions: </strong>Our results indicate that the density of stromal lymphocytic infiltrate might be a better predictor of PD-L1 positivity in early breast cancer than the molecular subtype and that the key to the optimization of PD-L1 as a biomarker in breast cancer lies in its interpretation in the context of other immune response markers.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":"193-204"},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138795689","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":"Immunocytochemical localization of calbindin-D28K, calretinin, and parvalbumin in the Mongolian gerbil (Meriones unguiculatus) visual cortex.","authors":"Jae-Rim Son, Xin-Yu Kuai, Chang-Jin Jeon","doi":"10.5603/FHC.a2023.0010","DOIUrl":"https://doi.org/10.5603/FHC.a2023.0010","url":null,"abstract":"<p><strong>Introduction: </strong>While most animals of the Muridae family are nocturnal, the gerbil displays diurnal activity and provides a useful model for visual system research. The purpose of this study was to investigate the localization of calcium-binding proteins (CBPs) in the visual cortex of the Mongolian gerbil (Meriones unguiculatus). We also compared the labeling of CBPs to those of gamma-aminobutyric acid (GABA)- and nitric oxide synthase (NOS)-containing neurons.</p><p><strong>Material and methods: </strong>The study was conducted on twelve adult Mongolian gerbils (3-4 months old). We used horseradish peroxidase immunocytochemistry and two-color fluorescence immunocytochemistry with conventional and confocal microscopy to assess CBPs localization in the visual cortex.</p><p><strong>Results: </strong>The highest density of calbindin-D28K (CB)- (34.18%) and parvalbumin (PV)-IR (37.51%) neurons was found in layer V, while the highest density of calretinin (CR)-IR (33.85%) neurons was found in layer II. The CB- (46.99%), CR- (44.88%), and PV-IR (50.17%) neurons mainly displayed a multipolar round/oval morphology. Two-color immunofluorescence revealed that only 16.67%, 14.16%, and 39.91% of the CB-, CR-, and PV-IR neurons, respectively, contained GABA. In addition, none of the CB-, CR-, and PV-IR neurons contained NOS.</p><p><strong>Conclusions: </strong>Our findings indicate that CB-, CR-, and PV-containing neurons in the Mongolian gerbil visual cortex are distributed abundantly and distinctively in specific layers and in a small population of GABAergic neurons but are limited to subpopulations that do not express NOS. These data provide a basis for the potential roles of CBP-containing neurons in the gerbil visual cortex.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":"61 2","pages":"81-97"},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10191724","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}
Lili Ji, Xiaojing Shi, Gaopin Wang, Huiping Wu, Zhansheng Hu
{"title":"Overexpressing six-transmembrane protein of prostate 2 (STAMP2) alleviates sepsis-induced acute lung injury probably by hindering M1 macrophage polarization via the NF-κB pathway.","authors":"Lili Ji, Xiaojing Shi, Gaopin Wang, Huiping Wu, Zhansheng Hu","doi":"10.5603/FHC.a2022.0032","DOIUrl":"https://doi.org/10.5603/FHC.a2022.0032","url":null,"abstract":"<p><strong>Introduction: </strong>Acute lung injury (ALI) is a major cause of death in sepsis patients. The Six-transmembrane protein of prostate 2 (STAMP2) is a key regulator of inflammation, while its role in septic ALI remains unclear.</p><p><strong>Material and methods: </strong>Male C57BL/6 mice were subjected to cecal ligation puncture (CLP) to induce experimental sepsis whereas lipopolysaccharide (LPS)-stimulated RAW 264.7 cells were used as the models of septic ALI in vivo and in vitro, respectively. Overexpression of STAMP2 in mouse lungs and RAW264.7 cells was performed with an adenoviral vector. We measured histological lung injury, lung wet/dry weight (W/D) ratio, and pulmonary myeloperoxidase (MPO) activity to assess lung injury extent. Cell counts in bronchoalveolar lavage fluid (BALF) were measured using Giemsa staining. The concentration of inflammatory factors was detected by enzyme-linked immunosorbent assay. The polarization of macrophages was evaluated by inducible nitric oxide synthase (iNOS) and F4/80 staining. The activation of cell apoptosis and NF-κB pathway was evaluated using Western blot, TUNEL staining, immunofluorescence, and immunohistochemistry.</p><p><strong>Results: </strong>Overexpression of STAMP2 alleviated CLP-induced lung injury of mice with decreased W/D ratio of the lung, and MPO activity in lung tissue. STAMP2 overexpression reduced the lung infiltration of inflammatory cells, and the levels of TNF-a, IL-6, and macrophage chemoattractant protein-1 (MCP-1) in BALF. Overexpressed STAMP2 inhibited macrophage M1 polarization in lung tissues as indicated by F4/80 and iNOS stainings in lung tissue. STAMP2 overexpression inhibited RAW 264.7 cell apoptosis by increasing Bcl-2 and decreasing Bax and cleaved-caspase 3 expression. Besides, STAMP2 overexpression suppressed nuclear factor κB (NF-κB) p65 pathway activation, as evidenced by reduced phosphorylation of IκBα, and phosphorylation and translocation of NF-κB p65. In vitro study further proved that STAMP2 overexpression suppressed the NF-κB pathway (IκBα/p65) in macrophages and decreased macrophage M1 polarization and M1-associated inflammatory factor production (TNF-a, IL-6, and MCP-1).</p><p><strong>Conclusions: </strong>Our study for the first time demonstrated that STAMP2 might be able to reduce inflammation in sepsis-induced ALI by inhibiting macrophage M1 polarization through repressing NF-κB signaling activation.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":"61 1","pages":"34-46"},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9200785","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}