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Background: Colorectal cancer is one of the most commonly diagnosed cancer and leading causes of cancer death worldwide. Fibrinogen-like protein 2 (FGL2), a member of the fibrinogen family, has been demonstrated as a regulator of immune cell functions in tumor microenvironment and might facilitate tumor progression. Aims: To study the expression and clinical significance of FGL2 in colon cancer. Methods: One hundred and fifty colon cancer patients diagnosed from January 2018 to January 2022 at the Second Hospital of Tianjin Medical University were enrolled in this study. The paraffin-embedded tissues were collected for detection of FGL2 protein and the surface markers of tumor infiltrating immune cells (TIICs), including CD4, CD8, CD20, CD68, and CD56 by using immunohistochemistry. The correlations of FGL2 expression level with the clinicopathological parameters and TIICs counting were analyzed. Results: Expression of FGL2 was upregulated in 68.7% of the colon cancer cases. Its expression level was correlated positively with the tumor size and TNM staging (all P0.05). Meanwhile, the expression level of FGL2 was associated with the cell counting of CD4
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Soluble fibrinogen-like protein 2 (sFGL2) , is an novel effector secreted by the CD4+CD25+CD127lowTregs cells and plays an important role in immunoregulation.It is critical for the maintenance of the activity and function of Tregs.It can induce the apoptosis of B cells, suppress the maturation of dendritic cells and suppress the activation and proliferation of T cells through the FcγRⅡB receptor.This review concluded the recent progress of the genes, structure, immunoregulatory effects of sFGL2, and discussed the clinical implications of sFGL2in hepatitis, autoimmunity, transplantation, tumors and atherosclerosis.
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Objective To investigate the therapeutic effect of silencing fibrinogen-like protein 2 (FGL2) gene on acute necrotic pancreatitis (ANP) mice.Methods Eighteen C57/BL mice were randomly divided into SO (sham operation) group,ANP group and Ad-FGL2-siRNA group carrying FGL2 siRNA adenovirus,with 6 in each group.Sodium taurocholate was retrogradely injected into the biliopancreatic ducts of the mice to induce ANP mice model.The mice in Ad-FGL2-siRNA group were injected intravenously in the tail vein with Ad-FGL2-siRNA befor the model establishment.The mice were sacrificed 6 h later,and then the pancreatic tissue and blood were collected.TNF-α and IL-1β expression were measured with ELISA,pancreatic tissue was examined with routine pathological examination,FGL2 mRNA and protein expression were measured with reverse transcription-PCR,western blotting and immunohistochemical staining,and cell apoptosis was assessed by TUNEL method.Results The pathological score of the pancreatic tissue in SO group,ANP group and Ad-FGL2-miRNA group was(1.33 ±0.21),(9.17 ±0.98) and (6.26 ±0.52),respectively.The serum TNF-α level in SO group,ANP group and Ad-FGL2-miRNA group was(63.8 ± 4.2),(240.4 ± 18.6)and(123.0 ± 10.3)ng/L,respectively.The serum IL-1β level was (43.6 ±4.4),(186.6 ± 18.7)and (92 ±10.9)ng/L.The mRNA expressions of FGL2 was 1.20 ±0.22,4.40 ± 1.21 and 2.15 ± 0.56.The protein expressions of FGL2 was 0.33 ± 0.08,1.23 ± 0.24 and 0.68 ± 0.09.The rate of FGL2 positive cells was (2.56 ± 0.31) ％,(15.10 ± 3.23) ％ and (8.68 ± 1.81) ％.The number of apoptotic cells was (4.51 ±1.21),(35.81 ± 4.11) and (11.79 ± 3.02) / × 200HPF,which in the ANP group was higher than that in SO group,and in the Ad-FGL2-siRNA group was significantly lower than that in ANP group and higher than that in SO group.All the differences were statistically significant (all P values ＜ 0.05),except that on the FGL2 mRNA expression between Ad-FGL2-siRNA group and SO group.Conclusions Silencing FGL2 gene may alleviate pancreatic injury in ANP by reducing the release of inflammatory factors and inhibiting cell apoptosis.
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Microthrombosis may be involved in the pathogenesis of cardiac microangiopathy due to diabetes. Recent studies have shown that fibrinogen-like protein 2 (fgl2) plays a pivotal role in microthrombosis in viral hepatitis, acute vascular xenograft rejection and cytokine-induced fetal loss syndrome. The current study was designed to examine the expression of fgl2 in microvascular endothelial cells and investigate the effects of microthrombi due to fgl2 on cardiac function and structure in rats with type 2 diabetes. Following induction of type 2 diabetes, 24 rats were observed dynamically. Fgl2 expression and related cardiac microthrombosis were examined. Local or circulating TNF-a was measured. Coronary flow (CF) per min was calculated as an index of cardiac microcirculation. Cardiac function and morphology were evaluated. It was found that Fgl2 was highly expressed in cardiac microvascular endothelial cells of rats with type 2 diabetes, which was promoted by local or circulating TNF-α. The Fgl2 expression was associated with cardiac hyaline microthrombosis. In parallel with the fgl2 expression, CF per min, cardiac diastolic or systolic function and cardiac morphology were aggravated to some extent. It was concluded that in rats with type 2 diabetes, microthrombosis due to fgl2 contributes to the impairment of cardiac diastolic or systolic function and morphological changes.
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To evaluate the role of murine fibrinogen like protein 2 (mfgl2) /fibroleukin in lung impairment in Severe acute respiratory syndrome (SARS), a murine SARS model induced by Murine hepatitis virus strain 3 (MHV-3) through trachea was established. Impressively, all the animals developed interstitial pneumonia with extensive hyaline membranes formation within alveoli, and presence of micro-vascular thrombosis in the pulmonary vessels. MHV-3 nucleocapsid gene transcripts were identified in multiple organs including lungs, spleen etc. As a representative proinflammatory gene, mfgl2 prothrombinase expression was evident in terminal and respiratory bronchioles, alveolar epithelia and infiltrated cells in the lungs associated with fibrin deposition and micro-vascular thrombosis. In summary, the established murine SARS model could mimic the pathologic characteristics of lungs in patients with SARS. Besides the physical damages due to virus replication in organs, the up-regulation of novel gene mfgl2 in lungs may play a vital role in the development of SARS associated lung damage.
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Objective:To construct hfgl 2 expression vector(pcDNA3.1-hfgl 2) and characterize the expression of hfgl 2 in CHO cells after transfection. Methods: Total RNA was extracted from chinese human peripheral blood monocyte cells,cDNA was obtained by reverse transcription,hfgl 2 cDNA was amplified and cloned into pcDNA3.1 and the orientation and the sequence were ensured by restriction endonucleases and sequencing assays.The recombinated plasmid was transfected into CHO cells,and the expression of hfgl 2 was detected by immunohistochemistry. Results:A 1.3 kb long target fragment was obtained and cloned into pcDNA3.1.The orientation and sequence are correct.hfgl 2 was only expressed in those cells transfected with pcDNA3.1-hfgl 2. Conclusion:hfgl 2 expression vector(pcDNA3.1-hfgl 2) has been successfully constructed.
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Objective: To construct and characterize GFP-mfgl 2 fusion protein expression plasmid (pEGFP-mfgl 2) and provide a direct and simplified methodology for primary assessment of the effect of mfgl 2 siRNA on the mfgl 2 gene expression. Methods: mfgl 2 cDNA was amplified from the mfgl 2 cDNA library pBluescript-m166 (pm166) of mouse genomic P1 plasmid and recloned into pEGFP-N2 upstream of GFP gene. The pEGFP-mfgl 2 was analyzed by restriction endonucleases BamH I and Hind III to ensure the orientation and the sequence. This fusion plasmid was then transfected into CHO cells and the fusion protein expression was observed by fluorescent microscope. Rusults: A 1.3 kb long cDNA was obtained. Restriction endonucleases and sequencing assays showed the correct orientation and sequence. After 24-48 hours transfection in CHO cells, the expression of pEGFP-mfgl 2 can be visualized through fluorescent microscope. Conclusion: pEGFP mfgl 2 has been constructed successfully. The recombinant vector can express GFP-mfgl 2 fusion protein. It provides a direct and simplified methodology for primary assessment of the effect of mfgl 2 siRNA on the mfgl 2 gene expression.
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Objective: To investigate the relationship of murine fibrinogen-like protein 2(mfgl2) / fibroleukin with pulmonary impairment in the murine model of severe acute respiratory syndrome(SARS).Methods: The Balb/cJ mice infected with murine hepatitis virus strain 3(MHV-3) through the trachea were observed for the pathological features and virus distribution in different organs.The expressions of both mfgl2 and fibrino in the lungs were determined by in situ hybridization and immunohistochemistry.Results: The MHV-3 infected mice developed typical interstitial pneumonia with extensive hyaline membrane formation in the alveoli,presented micro-vascular thrombosis in the pulmonary vessels and died within 5 days.MHV-3 virus replication was identified in all the organs observed.The specific expression of mfgl2 prothrombinase was noted in the terminal and respiratory bronchioles,alveolar epithelia and infiltrating cells.Conclusion: The characteristics of the pulmonary impairment of SARS in human can be properly simulated by the MHV-3 induced murine model of SARS.The up-regulation of the specific gene mfgl2 in the lungs involved in fibrino deposition and microvascular thrombosis may be largely responsible for SARS-associated pulmonary damages.