Expression of MCP-1 and TGF-β1 and its significance in early stage of obstructive jaundice in rats

Objective To investigate the expression of MCP-1 and TGF-β1 in early stage of ob-structive jaundice and explore its relation to liver correlated injury indexes in rats. Methods Fifty male Wistar rats were randomized into the control group, sham-operated group and biliary obstruction group. On day 10, serum ALT and BIL-T levels were determined in inferior caval blood and hepatic MDA was estimated in liver homogenates. Meanwhile, serum TGF-β1 level was measured by ELISA and the MCP-1 infiltration determined with immunohistochemistry. Results Serum ALT and BIL-T values were elevated. Meanwhile, the liver MDA content was increased. The positive expression of MCP-1 was augmented and serum TGF-β1 was over-expressed in the early stage after obstructive jaun-dice in rats. The hepatic MCP-1 expression had a positive correlation with the elevated ALT, BIL-T and MDA levels. However, the serum TGF-β1 content only had a positive correlation with ALT and BIL-T. Conclution Hepatic MCP-1 and serum TGF-β1 expression in the early stage after biliary tract obstruction is related to liver injury and extrahepatic cholestasis. Meanwhile, the hepatic MCP-1 ex-pression is correlated with hepatic oxidation stress. They have an important significance in liver injury in rats during the early period of obstructive jaundice.     

Latency and activation in the control of TGF-β

The biological activity of the transforming growth factor-'s (TGF-)³ is tightly controlled by their persistance in the extracellular compartment as latent complexes. Each of the three mammalian isoform genes encodes a product that is cleaved intracellularly to form two polypeptides, each of which dimerizes. Mature TGF-, a 24 kD homodimer, is noncovalently associated with the 80 kD latency-associated peptide (LAP). LAP is a fundamental component of TGF- that is required for its efficient secretion, prevents it from binding to ubiquitous cell surface receptors, and maintains its availability in a large extracellular reservoir that is readily accessed by activation. This latent TGF- complex (LTGF-) is secreted by all cells and is abundant both in circulating forms and bound to the extracellular matrix. Activation describes the collective events leading to the release of TGF-. Despite the importance of TGF- regulation of growth and differentiation in physiological and malignant tissue processes, remarkably little is known about the mechanisms of activationin situ. Recent studies of irradiated mammary gland reveal certain features of TGF-1 activation that may shed light on its regulation and potential roles in the normal and neoplastic mammary gland.     

Expression of HGF and TGF-β1 mRNA after partial hepatectomy in rats with liver cirrhosis

Hepatocyte growth factor (HGF) is a potent mitogen for the maturation of hepatocytes in vitro which plays a role in liver regeneration in vivo. In addition, transforming growth factor-₁ (TGF-₁) is also a potent regulator of liver regeneration. In attempting to clarify the mechanisms related to liver regeneration after partial hepatectomy, we investigated the expression of HGF and TGF-₁ in rats with liver cirrhosis (LC). A rat model of LC was prepared using carbon tetrachloride (CCl₄). The expression of HGF mRNA in both the LC and control groups showed a similar time-course with the highest expression seen at 18 h after a 70% hepatectomy. The expression of TGF-₁ mRNA peaked at 18 h after partial hepatectomy in the LC group and at 48 h in the control group. The 5-bromo-2'-deoxyuridine (BrdU) labeling index for the LC group at 24, 48, and 72 h after partial hepatectomy was 9.2%, 5.9%, and 1.8%, while for the control group it was 7.0%, 11.7%, and 6.8%, respectively. The BrdU labeling index in the LC group was thus suppressed earlier than that in the control group. We therefore postulate that regeneration of the remnant liver in the presence of LC accelerates immediately after partial hepatectomy, but the extent of regeneration is insufficient because of an early cessation due to an early expression of TGF-₁.     

Expression of fibronectin and TGF-ß1 mRNA and protein suggest altered regulation of extracellular matrix in degenerated disc tissue

We studied the distribution of fibronectin (a marker for active reparative connective tissue processes) and TGF-1 (a cytokine controlling the connective tissue metabolism) in intervertebral disc tissue from individuals of different age and various histomorphological evidence for tissue degeneration. The protein deposition was determined by immunohistochemistry on 30 complete cross-sections of lumbar spine obtained at autopsy (0–86 years) and 12 surgically removed disc samples. The mRNA expression was detected by non-radioactive in situ hybridization in the surgical material. All control experiments (blank and isotype controls in immunohistochemistry/sense controls in in situ hybridization) were negative. Immunohistochemically, we detected enhanced staining for fibronectin in both nuclear and anular tissues in areas with histological signs of mild-to-severe tissue degeneration (e.g., cleft formation and cell clustering) beginning with 16 years of age. Anular tissue showed less fibronectin staining than did nuclear areas. Fibronectin mRNA was detected mainly in nuclear cells by in situ hybridization corresponding to the protein staining indicating de novo synthesis. In parallel, TGF-1 was expressed by nuclear and occasional anular cells spatially associated with the fibronectin synthesizing cells. This was seen by both immunohistochemistry and in situ hybridization. This preliminary study provides evidence for a significant ongoing rearrangement of the extracellular matrix during disc degeneration, as monitored by enhanced fibronectin deposition that is produced by local disc cells. These cells also synthesize TGF-1, as shown by protein and mRNA expression. Since it is known that TGF-1 induces matrix alterations (by auto and paracrine stimulation of matrix synthesis), these observations suggest that the recently described disturbance of the matrix during disc degeneration may be induced by TGF-. This may offer new approaches to interfere with disc matrix alterations.     

Expression and significance of HIF-1α and ET-1 in gastrointestinal stromal tumors

Objective To explore the expression and the value of HIF-1α,and ET-1 in judging the prognosis of gastrointestinal stromal tumors (GISTs). Methods The expression of HIF-1α, and ET-1 protein was examined in 76 GISTs by immunohistochemistry S -P methods. Results There was a positive correlation between the expression of HIF-1 α and ET-1 ( P < 0.05 ). The positive expression rate of HIF-1 α and ET-1 was 73.68% (50/76) ,and 65.79% (50/76) respectively,which was related with histologicial grade, tumor diameter, infiltration and metastasis, nuclear division rating of GISTs ( P < 0.05 ), but had no relationship with patients' age, gender, initial position of the tumor ( P > 0.05 ). There was statistically sig-nificant difference in the expression of HIF-1 α and ET-1 in the following groups:among the three classes of very low-risk and low-risk, middle-risk, high-risk, bewteen the diameter < 2 cm and > 5 cm (P < 0.05). The more malignant degree and larger diameter, the more highly positive expression rate ( P < 0.05 ). The positive expression in the groups with infiltration and metastasis, and nuclear division ≥5/50 HP was sig-nificantly higher than the groups without infiltration and metastasis, and nuclear division < 5/50 HP (P < 0.05). Conclusion The expression of HIF-1α had a significant correlation with ET-1. HIF-1α,and ET-1 expression was closely related with the prognosis of GISTs,and can serve as important predictors for survival.     

Expression and significance of HIF-1α and ET-1 in gastrointestinal stromal tumors

Objective To explore the expression and the value of HIF-1α,and ET-1 in judging the prognosis of gastrointestinal stromal tumors (GISTs). Methods The expression of HIF-1α, and ET-1 protein was examined in 76 GISTs by immunohistochemistry S -P methods. Results There was a positive correlation between the expression of HIF-1 α and ET-1 ( P < 0.05 ). The positive expression rate of HIF-1 α and ET-1 was 73.68% (50/76) ,and 65.79% (50/76) respectively,which was related with histologicial grade, tumor diameter, infiltration and metastasis, nuclear division rating of GISTs ( P < 0.05 ), but had no relationship with patients' age, gender, initial position of the tumor ( P > 0.05 ). There was statistically sig-nificant difference in the expression of HIF-1 α and ET-1 in the following groups:among the three classes of very low-risk and low-risk, middle-risk, high-risk, bewteen the diameter < 2 cm and > 5 cm (P < 0.05). The more malignant degree and larger diameter, the more highly positive expression rate ( P < 0.05 ). The positive expression in the groups with infiltration and metastasis, and nuclear division ≥5/50 HP was sig-nificantly higher than the groups without infiltration and metastasis, and nuclear division < 5/50 HP (P < 0.05). Conclusion The expression of HIF-1α had a significant correlation with ET-1. HIF-1α,and ET-1 expression was closely related with the prognosis of GISTs,and can serve as important predictors for survival.     

Expression and significance of HIF-1α and ET-1 in gastrointestinal stromal tumors

Objective To explore the expression and the value of HIF-1α,and ET-1 in judging the prognosis of gastrointestinal stromal tumors (GISTs). Methods The expression of HIF-1α, and ET-1 protein was examined in 76 GISTs by immunohistochemistry S -P methods. Results There was a positive correlation between the expression of HIF-1 α and ET-1 ( P < 0.05 ). The positive expression rate of HIF-1 α and ET-1 was 73.68% (50/76) ,and 65.79% (50/76) respectively,which was related with histologicial grade, tumor diameter, infiltration and metastasis, nuclear division rating of GISTs ( P < 0.05 ), but had no relationship with patients' age, gender, initial position of the tumor ( P > 0.05 ). There was statistically sig-nificant difference in the expression of HIF-1 α and ET-1 in the following groups:among the three classes of very low-risk and low-risk, middle-risk, high-risk, bewteen the diameter < 2 cm and > 5 cm (P < 0.05). The more malignant degree and larger diameter, the more highly positive expression rate ( P < 0.05 ). The positive expression in the groups with infiltration and metastasis, and nuclear division ≥5/50 HP was sig-nificantly higher than the groups without infiltration and metastasis, and nuclear division < 5/50 HP (P < 0.05). Conclusion The expression of HIF-1α had a significant correlation with ET-1. HIF-1α,and ET-1 expression was closely related with the prognosis of GISTs,and can serve as important predictors for survival.     

Expression and significance of HIF-1α and ET-1 in gastrointestinal stromal tumors

Objective To explore the expression and the value of HIF-1α,and ET-1 in judging the prognosis of gastrointestinal stromal tumors (GISTs). Methods The expression of HIF-1α, and ET-1 protein was examined in 76 GISTs by immunohistochemistry S -P methods. Results There was a positive correlation between the expression of HIF-1 α and ET-1 ( P < 0.05 ). The positive expression rate of HIF-1 α and ET-1 was 73.68% (50/76) ,and 65.79% (50/76) respectively,which was related with histologicial grade, tumor diameter, infiltration and metastasis, nuclear division rating of GISTs ( P < 0.05 ), but had no relationship with patients' age, gender, initial position of the tumor ( P > 0.05 ). There was statistically sig-nificant difference in the expression of HIF-1 α and ET-1 in the following groups:among the three classes of very low-risk and low-risk, middle-risk, high-risk, bewteen the diameter < 2 cm and > 5 cm (P < 0.05). The more malignant degree and larger diameter, the more highly positive expression rate ( P < 0.05 ). The positive expression in the groups with infiltration and metastasis, and nuclear division ≥5/50 HP was sig-nificantly higher than the groups without infiltration and metastasis, and nuclear division < 5/50 HP (P < 0.05). Conclusion The expression of HIF-1α had a significant correlation with ET-1. HIF-1α,and ET-1 expression was closely related with the prognosis of GISTs,and can serve as important predictors for survival.     

Expression and significance of HIF-1α and ET-1 in gastrointestinal stromal tumors

Objective To explore the expression and the value of HIF-1α,and ET-1 in judging the prognosis of gastrointestinal stromal tumors (GISTs). Methods The expression of HIF-1α, and ET-1 protein was examined in 76 GISTs by immunohistochemistry S -P methods. Results There was a positive correlation between the expression of HIF-1 α and ET-1 ( P < 0.05 ). The positive expression rate of HIF-1 α and ET-1 was 73.68% (50/76) ,and 65.79% (50/76) respectively,which was related with histologicial grade, tumor diameter, infiltration and metastasis, nuclear division rating of GISTs ( P < 0.05 ), but had no relationship with patients' age, gender, initial position of the tumor ( P > 0.05 ). There was statistically sig-nificant difference in the expression of HIF-1 α and ET-1 in the following groups:among the three classes of very low-risk and low-risk, middle-risk, high-risk, bewteen the diameter < 2 cm and > 5 cm (P < 0.05). The more malignant degree and larger diameter, the more highly positive expression rate ( P < 0.05 ). The positive expression in the groups with infiltration and metastasis, and nuclear division ≥5/50 HP was sig-nificantly higher than the groups without infiltration and metastasis, and nuclear division < 5/50 HP (P < 0.05). Conclusion The expression of HIF-1α had a significant correlation with ET-1. HIF-1α,and ET-1 expression was closely related with the prognosis of GISTs,and can serve as important predictors for survival.     

Expression and significance of HIF-1α and ET-1 in gastrointestinal stromal tumors

Objective To explore the expression and the value of HIF-1α,and ET-1 in judging the prognosis of gastrointestinal stromal tumors (GISTs). Methods The expression of HIF-1α, and ET-1 protein was examined in 76 GISTs by immunohistochemistry S -P methods. Results There was a positive correlation between the expression of HIF-1 α and ET-1 ( P < 0.05 ). The positive expression rate of HIF-1 α and ET-1 was 73.68% (50/76) ,and 65.79% (50/76) respectively,which was related with histologicial grade, tumor diameter, infiltration and metastasis, nuclear division rating of GISTs ( P < 0.05 ), but had no relationship with patients' age, gender, initial position of the tumor ( P > 0.05 ). There was statistically sig-nificant difference in the expression of HIF-1 α and ET-1 in the following groups:among the three classes of very low-risk and low-risk, middle-risk, high-risk, bewteen the diameter < 2 cm and > 5 cm (P < 0.05). The more malignant degree and larger diameter, the more highly positive expression rate ( P < 0.05 ). The positive expression in the groups with infiltration and metastasis, and nuclear division ≥5/50 HP was sig-nificantly higher than the groups without infiltration and metastasis, and nuclear division < 5/50 HP (P < 0.05). Conclusion The expression of HIF-1α had a significant correlation with ET-1. HIF-1α,and ET-1 expression was closely related with the prognosis of GISTs,and can serve as important predictors for survival.     

Expression and significance of HIF-1α and ET-1 in gastrointestinal stromal tumors

Objective To explore the expression and the value of HIF-1α,and ET-1 in judging the prognosis of gastrointestinal stromal tumors (GISTs). Methods The expression of HIF-1α, and ET-1 protein was examined in 76 GISTs by immunohistochemistry S -P methods. Results There was a positive correlation between the expression of HIF-1 α and ET-1 ( P < 0.05 ). The positive expression rate of HIF-1 α and ET-1 was 73.68% (50/76) ,and 65.79% (50/76) respectively,which was related with histologicial grade, tumor diameter, infiltration and metastasis, nuclear division rating of GISTs ( P < 0.05 ), but had no relationship with patients' age, gender, initial position of the tumor ( P > 0.05 ). There was statistically sig-nificant difference in the expression of HIF-1 α and ET-1 in the following groups:among the three classes of very low-risk and low-risk, middle-risk, high-risk, bewteen the diameter < 2 cm and > 5 cm (P < 0.05). The more malignant degree and larger diameter, the more highly positive expression rate ( P < 0.05 ). The positive expression in the groups with infiltration and metastasis, and nuclear division ≥5/50 HP was sig-nificantly higher than the groups without infiltration and metastasis, and nuclear division < 5/50 HP (P < 0.05). Conclusion The expression of HIF-1α had a significant correlation with ET-1. HIF-1α,and ET-1 expression was closely related with the prognosis of GISTs,and can serve as important predictors for survival.     

Expression and significance of HIF-1α and ET-1 in gastrointestinal stromal tumors

Objective To explore the expression and the value of HIF-1α,and ET-1 in judging the prognosis of gastrointestinal stromal tumors (GISTs). Methods The expression of HIF-1α, and ET-1 protein was examined in 76 GISTs by immunohistochemistry S -P methods. Results There was a positive correlation between the expression of HIF-1 α and ET-1 ( P < 0.05 ). The positive expression rate of HIF-1 α and ET-1 was 73.68% (50/76) ,and 65.79% (50/76) respectively,which was related with histologicial grade, tumor diameter, infiltration and metastasis, nuclear division rating of GISTs ( P < 0.05 ), but had no relationship with patients' age, gender, initial position of the tumor ( P > 0.05 ). There was statistically sig-nificant difference in the expression of HIF-1 α and ET-1 in the following groups:among the three classes of very low-risk and low-risk, middle-risk, high-risk, bewteen the diameter < 2 cm and > 5 cm (P < 0.05). The more malignant degree and larger diameter, the more highly positive expression rate ( P < 0.05 ). The positive expression in the groups with infiltration and metastasis, and nuclear division ≥5/50 HP was sig-nificantly higher than the groups without infiltration and metastasis, and nuclear division < 5/50 HP (P < 0.05). Conclusion The expression of HIF-1α had a significant correlation with ET-1. HIF-1α,and ET-1 expression was closely related with the prognosis of GISTs,and can serve as important predictors for survival.     

Expression and significance of HIF-1α and ET-1 in gastrointestinal stromal tumors

Objective To explore the expression and the value of HIF-1α,and ET-1 in judging the prognosis of gastrointestinal stromal tumors (GISTs). Methods The expression of HIF-1α, and ET-1 protein was examined in 76 GISTs by immunohistochemistry S -P methods. Results There was a positive correlation between the expression of HIF-1 α and ET-1 ( P < 0.05 ). The positive expression rate of HIF-1 α and ET-1 was 73.68% (50/76) ,and 65.79% (50/76) respectively,which was related with histologicial grade, tumor diameter, infiltration and metastasis, nuclear division rating of GISTs ( P < 0.05 ), but had no relationship with patients' age, gender, initial position of the tumor ( P > 0.05 ). There was statistically sig-nificant difference in the expression of HIF-1 α and ET-1 in the following groups:among the three classes of very low-risk and low-risk, middle-risk, high-risk, bewteen the diameter < 2 cm and > 5 cm (P < 0.05). The more malignant degree and larger diameter, the more highly positive expression rate ( P < 0.05 ). The positive expression in the groups with infiltration and metastasis, and nuclear division ≥5/50 HP was sig-nificantly higher than the groups without infiltration and metastasis, and nuclear division < 5/50 HP (P < 0.05). Conclusion The expression of HIF-1α had a significant correlation with ET-1. HIF-1α,and ET-1 expression was closely related with the prognosis of GISTs,and can serve as important predictors for survival.     

Expression and significance of HIF-1α and ET-1 in gastrointestinal stromal tumors

Objective To explore the expression and the value of HIF-1α,and ET-1 in judging the prognosis of gastrointestinal stromal tumors (GISTs). Methods The expression of HIF-1α, and ET-1 protein was examined in 76 GISTs by immunohistochemistry S -P methods. Results There was a positive correlation between the expression of HIF-1 α and ET-1 ( P < 0.05 ). The positive expression rate of HIF-1 α and ET-1 was 73.68% (50/76) ,and 65.79% (50/76) respectively,which was related with histologicial grade, tumor diameter, infiltration and metastasis, nuclear division rating of GISTs ( P < 0.05 ), but had no relationship with patients' age, gender, initial position of the tumor ( P > 0.05 ). There was statistically sig-nificant difference in the expression of HIF-1 α and ET-1 in the following groups:among the three classes of very low-risk and low-risk, middle-risk, high-risk, bewteen the diameter < 2 cm and > 5 cm (P < 0.05). The more malignant degree and larger diameter, the more highly positive expression rate ( P < 0.05 ). The positive expression in the groups with infiltration and metastasis, and nuclear division ≥5/50 HP was sig-nificantly higher than the groups without infiltration and metastasis, and nuclear division < 5/50 HP (P < 0.05). Conclusion The expression of HIF-1α had a significant correlation with ET-1. HIF-1α,and ET-1 expression was closely related with the prognosis of GISTs,and can serve as important predictors for survival.     

Impact of PCI-neo-HGF on the expression of TGF-β1 and proliferation of glomerular mesangial cells in rats

肾小球系膜细胞(GMC)的过度增生是导致肾小球硬化及肾间质纤维化的重要机制之一[1].肝细胞生长因子(HGF)是一种多效性的细胞因子,其可通过加速细胞外基质降解,阻断小管上皮细胞转分化等实现对肾脏的保护[2-4].目前HGF对正常及增生的GMC是否有抑制作用尚不明确.本研究采用可在体内持续平稳表达的PCI-neo-HGF质粒进行研究[5],主要探讨HGF是否能抑制正常及脂多糖(LPS)刺激后的大鼠GMC的增生,以及这种作用是否与抑制转化生长因子β1(TGF-β1)的表达相关.