1.FUT8 modulates galectin-3 expression to regulate TGF-β1-mediated fibrosis of lung fibroblasts.
Wei Wei GAO ; Dai Jian LIU ; Xiao Meng ZHANG ; Qing Qing FENG ; Ying LIU
Journal of Southern Medical University 2022;42(8):1166-1173
OBJECTIVE:
To investigate the regulatory role of α-1, 6-fucosyltransferase (FUT8) in TGF-β1-induced proliferation, migration and fibrosis of human embryonic lung fibroblasts (MRC-5 cells) and explore the underlying molecular mechanism.
METHODS:
C57/BL6 mice were randomized into 4 groups for treatment with saline (control group), bleomycin, bleomycin+sh-NC or bleomycin+sh-FUT8, and pulmonary fibrosis was observed using Masson staining.MRC-5 cells were transfected with si-NC, FUT8 siRNA (si-FUT8), or both si-FUT8 and a galectin-3(Gal-3) overexpression plasmid (pcDNA3.1-Gal) prior to TGF-β1 treatment, and the changes in cell proliferation and migration were assessed using CCK-8 assay, BrdU assay, and wound healing assay; the changes in the expression levels of α-SMA, collagen I (COLIA1) and extracellular matrix fibronectin (FN) were detected with real-time quantitative PCR (RT-qPCR) and Western blotting.The interaction of FUT8 and Gal-3 was tested using coimmunoprecipitation (Co-IP) assay, and the effect of FUT8 silencing on Gal-3 and FAK/Akt signaling pathways was analyzed.
RESULTS:
FUT8 knockdown significantly reduced bleomycin-induced extracellular collagen deposition in the lung tissues of the mice.Silencing FUT8 obviously inhibited cell proliferation (P < 0.05) and migration mediated by TGF-β1.FUT8 knockdown down-regulated the mRNA and protein levels of α-SMA, COLIA1 and FN (P < 0.05) in the cells.Coimmunoprecipitation analysis showed that FUT8 interacted with Gal-3.Silencing FUT8 significantly down-regulated Gal-3 expression and inhibited the activation of the FAK/Akt signaling pathway (P < 0.05).Overexpression of Gal-3 obviously reversed the effects of FUT8 silencing on cell proliferation, migration and fibrosis (P < 0.05).
CONCLUSION
FUT8 regulates TGF-β1-induced proliferation, migration and fibrosis of MRC-5 cells by modulating Gal-3 expression, in which the FAK/Akt pathway may play a role.
Animals
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Bleomycin/metabolism*
;
Fibroblasts/metabolism*
;
Fibrosis
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Fucosyltransferases/metabolism*
;
Galectin 3/genetics*
;
Humans
;
Lung/metabolism*
;
Mice
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Transforming Growth Factor beta1/metabolism*
2.Development of heart failure risk prediction models based on a multi-marker approach using random forest algorithms.
Hui YUAN ; Xue-Song FAN ; Yang JIN ; Jian-Xun HE ; Yuan GUI ; Li-Ying SONG ; Yang SONG ; Qi SUN ; Wei CHEN
Chinese Medical Journal 2019;132(7):819-826
BACKGROUND:
The early identification of heart failure (HF) risk may favorably affect outcomes, and the combination of multiple biomarkers may provide a more comprehensive and valuable means for improving the risk of stratification. This study was conducted to assess the importance of individual cardiac biomarkers creatine kinase MB isoenzyme (CK-MB), B-type natriuretic peptide (BNP), galectin-3 (Gal-3) and soluble suppression of tumorigenicity-2 (sST2) for HF diagnosis, and the predictive performance of the combination of these four biomarkers was analyzed using random forest algorithms.
METHODS:
A total of 193 participants (80 patients with HF and 113 age- and gender-matched healthy controls) were included from June 2017 to December 2017. The correlation and regression analysis were conducted between cardiac biomarkers and echocardiographic parameters. The accuracy and importance of these predictor variables were assessed using random forest algorithms.
RESULTS:
Patients with HF exhibited significantly higher levels of CK-MB, BNP, Gal-3, and sST2. BNP exhibited a good independent predictive capacity for HF (AUC 0.956). However, CK-MB, sST2, and Gal-3 exhibited a modest diagnostic performance for HF, with an AUC of 0.709, 0.711, and 0.777, respectively. BNP was the most important variable, with a remarkably higher mean decrease accuracy and Gini. Furthermore, there was a general increase in predictive performance using the multi-marker model, and the sensitivity, specificity was 91.5% and 96.7%, respectively.
CONCLUSION
The random forest algorithm provides a robust method to assess the accuracy and importance of predictor variables. The combination of CK-MB, BNP, Gal-3, and sST2 achieves improvement in prediction accuracy for HF.
Adult
;
Algorithms
;
Biomarkers
;
blood
;
metabolism
;
Creatine Kinase, MB Form
;
blood
;
metabolism
;
Echocardiography
;
Female
;
Galectin 3
;
blood
;
metabolism
;
Heart Failure
;
blood
;
metabolism
;
pathology
;
Humans
;
Male
;
Middle Aged
;
Natriuretic Peptide, Brain
;
blood
;
metabolism
3.Effects of RhoA gene silencing by RNA interference on invasion of tongue carcinoma.
Zhenggang CHEN ; Yong-ping TANG ; Lei TONG ; Ying WANG ; Yuan ZHOU ; Qimin WANG ; Jinhong HAN ; Zongxuan HE ; Yixiang LIAO ; Bing FAN ; Rong-hai ZOU ; Jian ZHANG ; Xiaofeng SUN ; Guoxin YAN
West China Journal of Stomatology 2016;34(2):183-188
OBJECTIVETo study the effects of RhoA down-regulation by RNA interference on the invasion of tongue carcinoma Tca8113 and SCC-4.
METHODSDetermination of the human RhoA sequence as well as the design and constructionof a short specific small interfering RNAs (siRNA) were performed. The siRNA of RhoA gene was transfected into humantongue squamous cell carcinoma Tca8113 and SCC-4 cells line by Lipofectamine 2000. Quantitative real-time polymerasechain reaction was used to examine the mRNA expressionlevels of RhoA. Protein expressions of mRNA, galectin-3,and matrix metalloproteinase (MMP)-9 were evaluated byWestern blot. Transwell invasion assay was performed toassess the invasion ability of tongue carcinoma.
RESULTSRhoA expressions in Tca8113 and SCC-4 cells were reducedsignificantly after transfection of RhoA-siRNA. Protein levels f galectin-3 and MVP-9 were also down-regulated significantly. Invasion ability was inhibited as well.
CONCLUSIONRhoA-siRNA can effectively inhibit RhoA expression in Tca8113 and SCC-4 cells. The invasion ability of tongue carcinoma cells decreased with down-regulation of the protein expressions of galectin-3 and MMP-9, indicating that RhoA-siRNA can inhibit invasion of tongue carcinoma. Results show that RhoA may play an important role in the processes of invasion and metastasis of tongue carcinoma.
Carcinoma, Squamous Cell ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Down-Regulation ; Galectin 3 ; metabolism ; Gene Silencing ; Humans ; Matrix Metalloproteinase 9 ; metabolism ; RNA Interference ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Tongue Neoplasms ; genetics ; metabolism ; pathology ; Transfection
4.Relationship between serum 25-hydroxyl-vitamin D3 levels and galectin-3 levels in serum and bronchoalveolar lavage fluid in children with asthma.
Kun JIANG ; Xiao-Xia LU ; Ying WANG ; He-Bin CHEN ; Lin-Hua SHU
Chinese Journal of Contemporary Pediatrics 2015;17(12):1301-1305
OBJECTIVETo investigate the changes of the levels of galectin-3 (Gal-3) in serum and bronchoalveolar lavage fluid (BALF) of children with asthma whose have different serum levels of 25-hydroxyl-vitamin D₃[25(OH)D₃].
METHODSFifty children with asthma between January 2013 and December 2014 were enrolled as the asthma group, and they were classified into 25(OH)D₃sufficient (n=7), insufficient (n=12) and deficient subgroups (n=31) according to the serum levels of 25(OH)D₃. Twenty children with abnormal airway or tracheal foreign bodies served as the control group. The levels of 25(OH)D₃, Gal-3 and total IgE in serum and Gal-3 levels in BALF were measured using ELISA.
RESULTThe serum levels of 25(OH)D₃in the asthma group were lower than in the control group (P<0.05). The 25(OH)D₃deficient subgroup displayed the highest percentages of neutrophils, eosinophils and epithelial cells in BALF, followed by the 25(OH)D₃insufficient subgroup and the 25(OH)D₃sufficient subgroup (P<0.05). The percentages of neutrophils, eosinophils and epithelial cells in BALF in the three subgroups were all higher than in the control group (P<0.05). In children with asthma, serum levels of 25(OH)D₃were negatively correlated with the percentages of neutrophils, eosinophils and epithelial cells in BALF (r=-0.683, -0.795 and -0.670 respectively; P<0.05); and a negative correlation was also seen between serum 25(OH)D₃levels and serum Gal-3 and total IgE levels (r=-0.759 and -0.875 respectively; P<0.05).
CONCLUSIONSThe children with asthma have low serum levels of 25(OH)D₃. 25(OH)D₃and Gal-3 may be involved in the airway inflammation and the development of asthma.
Asthma ; etiology ; metabolism ; Bronchoalveolar Lavage Fluid ; chemistry ; Child ; Child, Preschool ; Female ; Galectin 3 ; analysis ; blood ; physiology ; Humans ; Immunoglobulin E ; blood ; Infant ; Male ; Vitamin D ; analogs & derivatives ; blood ; physiology
5.Galectin-3 expression in peripheral blood mononuclear cells of chronic hepatitis B patients treated with pegylated interferon alpha-2a.
Yi LI ; Long YU ; Xiaoling WU
Chinese Journal of Hepatology 2014;22(5):336-339
OBJECTIVETo study the relationship between therapeutic efficacy of pegylated interferon alpha-2a (Peg-IFNa-2a) in patients with chronic hepatitis B (CHB) and expression of Galectin-3 in peripheral blood mononuclear cells (PBMCs).
METHODSFifty CHB patients treated with a 48-week course of Peg-IFNa-2a (180 mug/week, subcutaneous) were divided into groups according to treatment response, with 14 patients in the 24-week responder group, 21 patients in the 48-week responder group and 15 patients in the non-responder groups. Twenty healthy volunteers served as the normal control group. Gene and protein expression of Galectin-3 in PBMCs was detected by PCR and westen blotting.
RESULTSPBMC expression of Galectin-3 was significantly higher in the effective treatment (responders) group compared to the control group and the non-responder group. In addition, the 24-week responders had significantly higher than the 48-week responders, and the 48-week responders had significantly higher Galectin-3 expression than the non-responders at 24 weeks.
CONCLUSIONPeg-IFNa-2a may inhibit HBV DNA replication by up-regulating the expression of Galectin-3 in PBMCs.
Adult ; Antiviral Agents ; therapeutic use ; Case-Control Studies ; Female ; Galectin 3 ; metabolism ; Hepatitis B, Chronic ; drug therapy ; metabolism ; Humans ; Interferon-alpha ; therapeutic use ; Leukocytes, Mononuclear ; metabolism ; Male ; Polyethylene Glycols ; therapeutic use ; Recombinant Proteins ; therapeutic use ; Treatment Outcome ; Young Adult
6.Vasculogenic mimicry in laryngeal squamous cell carcinoma and its clinicopathological significance.
Shiwu WU ; Lan YU ; Lei ZHOU ; Zenong CHENG ; Danna WANG
Journal of Biomedical Engineering 2014;31(4):865-869
The present paper aims to investigate whether or not vasculogenic mimicry (VM) exists in laryngeal squamous cell carcinoma (LSCC), and to elucidate its relationship to microvessel density (MVD), galectin-3 (Gal-3) expression, and clinicopathological factors of patients with LSCC. VM, score of MVD and expression of Gal-3 protein were detected by immunohistochemistry and histochemistry in 83 specimens of LSCC tissue and 20 specimens of normal laryngeal tissue. The positive rate of VM in normal laryngeal tissues was 0%, and was 33.7% in LSCC tissues. There was a significant difference between the two groups (P<0. 01). VM or MVD was significantly related to differentiation, pTNM stages and lymph node metastasis of LSCC (P<0.05), but not to age, gender and tumor site (P>0. 05). And there was a positive correlation between every two of VM, score of MVD, and Gal-3 protein (P< 0. 05). The results suggest that expression of Gal-3 protein may be related to the initiation, angiogenesis and VM formation in LSCC; And VM, angiogenesis and Gal-3 protein may be involved in the development, invasion and metastasis of LSCC.
Carcinoma, Squamous Cell
;
blood supply
;
Galectin 3
;
metabolism
;
Head and Neck Neoplasms
;
blood supply
;
Humans
;
Immunohistochemistry
;
Laryngeal Neoplasms
;
blood supply
;
Lymphatic Metastasis
;
Neovascularization, Pathologic
;
Prognosis
7.Diffuse Follicular Variant of Papillary Thyroid Carcinoma in a 69-Year-old Man with Extensive Extrathyroidal Extension: A Case Report.
Yoon Jin CHA ; Hang Seok CHANG ; Soon Won HONG
Journal of Korean Medical Science 2013;28(3):480-484
Diffuse follicular variant papillary thyroid carcinoma (DFVPTC) is a rare variant papillary thyroid carcinoma. DFVPTC typically occurs in young females, extensively involves one lobe or both lobes entirely with frequent nodal metastasis and vascular invasion. In contrast to the other subtypes of follicular variant, DFVPTC has biologically aggressive behavior. We present a case of DFVPTC arising in a 69-yr-old male patient. He presented hoarseness for a few months. Following diagnosis of malignancy on aspiration cytology, total thyroidectomy with neck dissection was performed. The tumor involved both lobes of thyroid, encroaching the surrounding structures including tracheal cartilage and esophagus. Multiple lymph node metastasis and vascular invasion were also found. The patient passed away due to the unexplained bleeding of surgical site.
Aged
;
Antigens, CD56/metabolism
;
Carcinoma, Papillary, Follicular/*diagnosis/pathology/surgery
;
Galectin 3/metabolism
;
Humans
;
Immunohistochemistry
;
Keratin-19/metabolism
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Lymph Nodes/pathology
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Lymphatic Metastasis
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Male
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Thyroid Neoplasms/*diagnosis/pathology/surgery
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Thyroidectomy
;
Tomography, X-Ray Computed
8.Expression of Gal-3 and CD82/KAI1 proteins in non-small cell lung cancer and their clinical significance.
Shi-wu WU ; Lan YU ; Lei ZHOU ; Ze-nong CHENG ; Yi-sheng TAO
Chinese Journal of Oncology 2013;35(2):124-128
OBJECTIVETo study the expression of galectin 3 (Gal-3) and CD82/KAI1 proteins in non-small cell lung cancer (NSCLC) and the correlation between their expression and clinical significance.
METHODSThe expression of Gal-3 and CD82/KAI1 proteins was detected by immunohistochemistry in 160 specimens of NSCLC and 20 specimens of normal lung tissue.
RESULTSThe positive rates of Gal-3 and CD82/KAI1 proteins in the NSCLC were 63.8% and 37.5%, respectively, the positive rates of Gal-3 and CD82/KAI1 proteins in the normal lung tissue were 25.0% and 95.0%, respectively, and there was a significant difference between the two groups (P < 0.01). The expression of Gal-3 and CD82/KAI1 proteins was significantly correlated with the grade of tumor, lymph node metastasis, and pathological-TNM stages (all P < 0.05). Spearman analysis showed that there was a negative correlation between expressions of Gal-3 and CD82/KAI1 in NSCLC (r = -0.732, P < 0.01). Overexpression of Gal-3 and low expression of CD82/KAI1 were related to poor prognosis: the survival rate was significantly lower in the positive Gal-3 group (survival time: 23.0 ± 17.5 months) than that in the negative group (survival time: 71.6 ± 21.6 months) (P < 0.01). The survival rates of the CD82/KAI1-positive group (survival time: 72.5 ± 19.5 months) and CD82/KAI1-negative group (survival time: 21.6 ± 16.1 months) were significantly different (P < 0.01). Multivariate analysis indicated that pTNM stage and positive expression of Gal-3 and CD82/KAI1 are independent prognostic factors of NSCLC (P < 0.01).
CONCLUSIONSThe expression of Gal-3 and CD82/KAI1 may be related to the initiation, development and metastasis of NSCLC. Combined detection of Gal-3 and CD82/KAI1 has an important role in predicting the progression and prognosis of NSCLC.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; Female ; Galectin 3 ; metabolism ; Humans ; Kangai-1 Protein ; metabolism ; Lung Neoplasms ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Proportional Hazards Models ; Survival Rate
9.Expression and prognostic significance of galectin-1 and galectin-3 in benign nevi and melanomas.
Zhong-wu LI ; Yan WANG ; Wei-cheng XUE ; Lu SI ; Chuan-liang CUI ; Deng-feng CAO ; Li-Xin ZHOU ; Jun GUO ; Ai-ping LU
Chinese Journal of Pathology 2013;42(12):801-805
OBJECTIVETo study the expression and prognostic significance of galectin-1 and galectin-3 in different melanocytic lesions.
METHODSThe expression of galectin-1 and galectin-3 in 39 cases of benign nevus, 58 cases of primary cutaneous melanoma, 24 cases of primary mucosal melanoma, 69 cases of melanoma with lymph node metastasis and 8 cases of melanoma with distant metastasis were studied by immunohistochemistry and tissue microarray.
RESULTSThe expression of galectin-1 and galectin-3 was higher in benign nevi than in melanomas (P < 0.01). The nuclear expression of galectin-3 was higher in primary cutaneous melanomas than in primary mucosal melanomas or melanomas with metastases (P < 0.01, respectively). The expression correlated with age of patients (P < 0.05), necrosis (P < 0.05) and survival time (P < 0.01). Clark's level also correlated with survival time in patients with cutaneous melanomas (P = 0.037). TNM staging was the only independent prognostic factor for melanomas (P < 0.01).
CONCLUSIONSThe expression of galectin-1 and galectin-3 is decreased in melanomas. The decrease in nuclear expression of galectin-3 may represent a poor prognostic factor for melanomas. TNM staging is an independent prognostic factor which influences the survival time.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Galectin 1 ; metabolism ; Galectin 3 ; metabolism ; Humans ; Immunohistochemistry ; Liver Neoplasms ; secondary ; Lung Neoplasms ; secondary ; Lymphatic Metastasis ; Male ; Melanoma ; metabolism ; pathology ; secondary ; Middle Aged ; Nasal Mucosa ; metabolism ; Neoplasm Staging ; Nevus ; metabolism ; pathology ; Skin Neoplasms ; metabolism ; pathology ; Survival Rate ; Young Adult
10.Detection of galectin-3 in both serum and tissue for early diagnosis of thyroid carcinoma.
Gang XUE ; Junchao LIU ; Jing HUANG ; Jing ZHANG ; Wenjing ZHANG ; Jingfang WU ; Xiaoling SHANG
Journal of Southern Medical University 2013;33(7):1027-1030
OBJECTIVETo investigate the levels of galectin-3 in the serum and surgical specimens from patients with malignant and benign thyroid lesions and explore their clinical significance.
METHODSSerum samples were collected from 159 patients with thyroid neoplasms and 16 normal subjects for detection of galectin-3 level using ELISA. The expressions of galectin-3 protein and mRNA were also detected in the surgical specimens by immunohistochemistry and in situ hybridization.
RESULTSGalectin-3 protein and mRNA were expressed at a rate of 96.67% in 66 cases of papillary thyroid carcinoma, 83.33% in 6 cases of follicular thyroid carcinoma, 16.67% in 36 cases of papillary hyperplasia, and 11.74% in 51 cases of thyroid adenoma. The expression level of galectin-3 mRNA was slightly lower than but positively correlated with its protein expression. Patients with thyroid carcinoma had significantly higher serum concentration of galectin-3 than those with benign thyroid lesions (papillary hyperplasia and thyroid adenoma) and normal subjects (P<0.001). In patients with papillary thyroid carcinoma, galectin-3 positivity in the tumor tissue was associated with a significantly higher serum galectin-3 level in comparison with the negative cases (P<0.05).
CONCLUSIONDetection of galectin-3 in both the serum and surgical specimens can improve the diagnosis rate of thyroid carcinoma.
Adult ; Aged ; Case-Control Studies ; Early Detection of Cancer ; Female ; Galectin 3 ; blood ; metabolism ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Thyroid Neoplasms ; blood ; diagnosis ; metabolism ; Young Adult

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