Immunolocalización de s100a4 y α-sma en tejidos gingivales de pacientes con hipertrofia gingival por tratamiento ortodóntico: estudio preliminar / Immunolocalization of s100a4 and α-sma in gingival tissues of patients with gingival hypertrophy due to orthodontic treatment: preliminary study

Objective: to determine the presence and distribution of markers of the epithelialmesenchymal transition (EMT) (S-100A4 and alpha-smooth muscle actin-α-SMA) in gingival tissues of patients affected by Gingival hypertrophy (GH) due to orthodontics.GH is an exaggerated increase in gingival tissue whose pathogenesis is unknown. However, it has been reported that the epithelial-mesenchymal transition as a process involved in other types of GH. Materials and methods: descriptive study that included the analysis of gingival tissues of healthy individuals (n = 6) and patients with GH by orthodontic treatment (n = 6). Before gingival surgery, the patients underwent a periodontal hygiene phase. The gingival tissue samples obtained were processed and embedded in paraffin. The cuts were made with a microtome and deposited on polysine adhesion slides. Histological hematoxylin-eosin staining was performed.The identification and location of S-100A4 and α-SMA markers was determined by immunohistochemistry with monoclonal antibodies. The reading of the findings was carried out by oral pathologists. Results: in healthy individuals, an S100A4 label was observed in Langerhans cells, while α-SMA was identified in the vascular endothelium of all samples analysed. However, in patients with GH due to orthodontics, they registered an intense staining of S100A4 in gingival fibroblasts, Langerhans cells, vascular endothelium, and areas adjacent to the rupture of blood vessel. α-SMA expression in GO was detected in the vascular endothelium and gingival fibroblasts. Conclusion: the differential immunostaining of EMT markers in gingival tissues of patients with orthodontic GH suggests an eventual role of EMT in the pathogenesis of this pathology..Au

Objective: to determine the presence and distribution of markers of the epithelialmesenchymal transition (EMT) (S-100A4 and alpha-smooth muscle actin-α-SMA) in gingival tissues of patients affected by Gingival hypertrophy (GH) due to orthodontics. GH is an exaggerated increase in gingival tissue whose pathogenesis is unknown. However, it has been reported that the epithelial-mesenchymal transition as a process involved in other types of GH. Materials and methods: descriptive study that included the analysis of gingival tissues of healthy individuals (n = 6) and patients with GH by orthodontic treatment (n = 6). Before gingival surgery, the patients underwent a periodontal hygiene phase. The gingival tissue samples obtained were processed and embedded in paraffin. The cuts were made with a microtome and deposited on polysine adhesion slides. Histological hematoxylin-eosin staining was performed. The identification and location of S-100A4 and α-SMA markers was determined by immunohistochemistry with monoclonal antibodies. The reading of the findings was carried out by oral pathologists. Results: in healthy individuals, an S100A4 label was observed in Langerhans cells, while α-SMA was identified in the vascular endothelium of all samples analysed. However, in patients with GH due to orthodontics, they registered an intense staining of S100A4 in gingival fibroblasts, Langerhans cells, vascular endothelium, and areas adjacent to the rupture of blood vessel. α-SMA expression in GO was detected in the vascular endothelium and gingival fibroblasts. Conclusion: the differential immunostaining of EMT markers in gingival tissues of patients with orthodontic GH suggests an eventual role of EMT in the pathogenesis of this pathology..Au

S100A4 Gene is Crucial for Methionine-Choline-Deficient Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice

PURPOSE: To explore the influence of S100 calcium binding protein A4 (S100A4) knockout (KO) on methionine-choline-deficient (MCD) diet-induced non-alcoholic fatty liver disease (NAFLD) in mice. MATERIALS AND METHODS: S100A4 KO mice (n=20) and their wild-type (WT) counterparts (n=20) were randomly divided into KO/MCD, Ko/methionine-choline-sufficient (MCS), WT/MCD, and WT/MCS groups. After 8 weeks of feeding, blood lipid and liver function-related indexes were measured. HE, Oil Red O, and Masson stainings were used to observe the changes of liver histopathology. Additionally, expressions of S100A4 and proinflammatory and profibrogenic cytokines were detected by qRT-PCR and Western blot, while hepatocyte apoptosis was revealed by TUNEL staining. RESULTS: Serum levels of aminotransferase, aspartate aminotransferase, triglyceride, and total cholesterol in mice were increased after 8-week MCD feeding, and hepatocytes performed varying balloon-like changes with increased inflammatory cell infiltration and collagen fibers; however, these effects were improved in mice of KO/MCD group. Meanwhile, total NAFLD activity scores and fibrosis were lower compared to WT+MCD group. Compared to WT/MCS group, S100A4 expression in liver tissue of WT/MCD group was enhanced. The expression of proinflammatory (TNF-α, IL-1β, IL-6) and profibrogenic cytokines (TGF-β1, COL1A1, α-SMA) in MCD-induced NAFLD mice were increased, as well as apoptotic index (AI). For MCD group, the expressions of proinflammatory and profibrogenic cytokines and AI in KO mice were lower than those of WT mice. CONCLUSION: S100A4 was detected to be upregulated in NAFLD, while S100A4 KO alleviated liver fibrosis and inflammation, in addition to inhibiting hepatocyte apoptosis.

Mechanism of recombinant human S100 calcium binding protein A4 inducing vascular endothelial growth factors in rheumatoid arthritis fibroblast-like synoviocytes / 中华创伤骨科杂志

Objective To investigate the mechanism of inducing production of vascular endothelial growth factors (VEGF) by recombinant human S100 calcium binding protein A4 (rhS100A4) in rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs).Methods Synovial tissue was sampled from the patients with rheumatoid arthritis (RA) undergoing knee arthroplasty for in vitro culture of RAFLSs.CCK-8 assay was conducted to detect the effect of rhS100A4 and the effect of its interaction with Rapamycin (Rap),an inhibitor of mammalian rapamycin target 1 (mTORC1) signaling pathway,on the proliferation of RAFLSs.The effects of rhS100A4 and its interaction with Rap on the expression of VEGF in RAFLSs were detected by immunofluorescence.After rhS100A4 and its cooperation with Rap stimulated the conditioned medium (CM)produced by RAFLSs,the effect of CM on formation of lumen in human unbilical vein endothelial cells (HUVECs) in vitro was observed to detect the angiogenic ability of rhS100A4.Western blot was used to detect the effect of rhS100A4 on the phosphorylation of downstream ribosomal protein S6 (S6) in the mTORC1 signaling pathway in RAFLSs and to analyze the effects of rhS100A4 and Rap on phosphorylation of S6 protein and expression of VEGF protein in RAFLSs.Results rhS100A4 promoted cell proliferation and expression of VEGF protein in RAFLSs,and the CM formed by rhS100A4 promoted HUVECs to form blood vessels in vitro.Rap inhibited the above biological effects of rhS100A4,rhS100A4 activated the downstream protein S6 in the mTORC1 signaling pathway in RAFLSs cells to increase their phosphorylation levels.The effects of rhS100A4 on the phosphorylation of S6 protein and on the expression of VEGF protein in RAFLSs were inhibited by Rap.Conclusion rhS10OA4 promotes production of VEGF in RAFLSs by activating the mTORC 1 signaling pathway.

Expression of S100A4 in synovium of patients with rheumatoid arthritis and its effect on angiogenesis of fibroblast-like synoviocytes by secreting VEGF / 中国病理生理杂志

AIM:To study the expression level of S100 calcium-binding protein A4 (S100A4) in synovial tissue of the knee joint in rheumatoid arthritis (RA) patients and normal persons, and the effect of S100A4 on the angiogenesis induced by rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs).METHODS:The synovial tissue was taken from the knee joint of the RA patients (RA group) and the normal persons (control group).The protein expression of S100A4 and vascular endothelial growth factor (VEGF) in the synovial tissue of the 2 groups was observed by immunohistochemistry.RAFLSs were isolated from synovial tissue of patients with active RA.ELISA was used to detect the effect of S100A4 on the secretion of VEGF by RAFLSs.The effect of S100A4 on the angiogenesis of HUVECs cultured with conditioned medium from RAFLSs was also detected.RESULTS:The protein of S100A4 and VEGF was highly expressed in the synovial tissues of RA group (P<0.05).rhS100A4 significantly stimulated the secretion of VEGF in RAFLSs in a time-and dose-dependent manner (P<0.05).Cultured with conditioned medium from RAFLSs, rhS100A4 significantly promoted HUVECs to form tube-like structures in vitro.CONCLUSION:S100A4 protein is highly expressed in synovial tissue of the knee joint in RA patients, and S100A4 stimulates synovial angiogenesis by promoting RAFLSs to generate VEGF, indicating that S100A4 may be used as a potential target for the treatment of RA.

S100 calcium binding protein A4 expression and signiifcance in gastric cancer / 中国癌症杂志

Background and purpose:This study investigated the relationship between (S100 calcium-binding protein A4, S100A4) in chronic gastritis, intestinal metaplasia, dysplasia adenomatous, normal tissue tissue samples and expression in gastric cancer and clinical characteristics. Methods:HE staining of the use of gastric specimens taken for histopathological diagnosis;using immunohistochemistry to detect the expression of tissue S100A4 protein;qRT-PCR was used to detect mRNA expression of S100A4 gene;Western Blot detection of S100A4 gene encoding protein. Kaplan-Meier survival curves were used to distinguish and compare survival. Results:S100A4 protein and mRNA expression gradually increased in the following order:normal tissue