AIM： To investigate the role of small intestinal carcinoid tumor-derived fibrotic mediators, TGFβ1 and CTGF, in the mediation of fibrosis via activation of an ＂intestinal＂ stellate cell. METHODS： GI carcinoid tum...AIM： To investigate the role of small intestinal carcinoid tumor-derived fibrotic mediators, TGFβ1 and CTGF, in the mediation of fibrosis via activation of an ＂intestinal＂ stellate cell. METHODS： GI carcinoid tumors were collected for Q RT-PCR analysis of CTGF and TGFβ1. Markers of stellate cell desmoplasia were identified in peritoneal fibrosis by immunohistochemistry and stellate cells cultured from fresh resected fibrotic tissue. CTGF and TGFβ1 were evaluated using quantitative tissue array profiling （AQUA analysis） in a GI carcinoid tissue microarray （TMA） with immunostaining and correlated with clinical and histologically documented fibrosis. Serum CTGF was analyzed using a sandwich ELISA assay. RESULTS： Message levels of both CTGF and TGFβ1 in SI carcinoid tumors were significantly increased （〉 2-fold, P 〈 0.05） versus normal mucosa and gastric （non-fibrotic） carcinoids. Activated stellate cells and markers of stellate cell-mediated fibrosis （vimentin, desmin） were identified in histological fibrosis. An intestinal stellate cell was immunocytochemically and biochemically characterized and its TGFβ1 （10-7M） initiated CTGF transcription response （〉 3-fold, P 〈 0.05） demonstrated. In SI carcinoid tumor patients with documented fibrosis, TMA analysis demonstrated higher CTGF immunostaining （AQUA Score： 92 ± 8, P 〈0.05）, as well as elevated TGFβ1 （90.6 ± 4.4, P 〈 0.05）. Plasma CTGF （normal 12.5 ± 2.6 ng/mL） was increased in SI carcinoid tumor patients （31 ± 10 ng/mL, P 〈 0.05） compared to non-fibrotic GI carcinoids （〈 15 ng/mL） CONCLUSION： SI carcinoid tumor fibrosis is a CTGF/ TGFβl-mediated stellate cell-driven fibrotic response. The delineation of the biology of fibrosis will facilitate diagnosis and enable development of agents to obviate its local and systemic complications.展开更多
Summary： The activation of hepatic stellate cells （HSCs） and their transformation to myofibroblasts are the key steps in the pathological progress of liver fibrosis. The transforming growth factor-J3 （TGFβ）/Smad...Summary： The activation of hepatic stellate cells （HSCs） and their transformation to myofibroblasts are the key steps in the pathological progress of liver fibrosis. The transforming growth factor-J3 （TGFβ）/Smad pathway is involved in the proliferation and collagen synthesis of HSCs. This study aimed to examine the effect of the protease inhibitor MG132 on the signaling pathway of TGFβ/Smad in HSC-T6 cells and seek a novel therapeutic approach for liver fibrosis. The HSC-T6 cells were treated with MG132 at different concentrations （0-10 maol/L）. Cell proliferation was detected by MTT method. The mRNA and protein expression levels of TGFI31, Smad3 and Smad7 were determined in HSC-T6 cells by real-time PCR and Western blotting, respectively, after treatment with MG132 at different con- centrations （1, 2, 3 μtmol/L） or RPMI1640 alone （serving as control）. The results showed that MG132 could inhibit the proliferation of HSC-T6 cells in a dose-dependent manner, and the IC50 of MG132 was 6.84 μmol/L. After treatment with MG132 at 1, 2 or 3 nol/L for 24 h, the mRNA expression levels of TGF-β1 and Smad3 were significantly decreased （P〈0.05）, but the Smad7 mRNA expression had no significant change （P〉0.05）. There was also a significant decrease in the protein expression level of TGF-β1 and Smad3 （P〈0.05）. However, the expression of Smad7 protein was substantially increased when compared with the control group （P〈0.05）. It was concluded that the inhibition of TGFi/Smad pathway in HSC-T6 cells by MG132 can reduce the production of profibrosis factors （TGFI31, Smad3） and promote the expression of anti-fibrosis factor （Smad7）, suggesting that MG132 may become a po- tential therapeutic alternative for liver fibrosis.展开更多
We often eat more than our body needs. We live in an environment where high calorie food is abundant and physical activities are limited. Living in this environment, maintaining healthy bodyweight becomes challenging ...We often eat more than our body needs. We live in an environment where high calorie food is abundant and physical activities are limited. Living in this environment, maintaining healthy bodyweight becomes challenging and obesity becomes a social burden. Why do we continue to eat even after the metabolic needs are satisfied？ Feeding is an ancient behavior essential to survive. Thus the mechanisms to regulate appetite, energy expenditure, and energy storage are well conserved throughout animals. Based on this conservation, we study why we fail to control appetite using a simple genetic model system C. elegans. We have discovered certain genetic components that when misregulated have animals eat more and store more fat. In this review we discuss how these genes work in the appetite control circuit to ultimately understand overall appetite control behavior. We will also briefly discuss how social influence affects feeding regardless of the metabolic status of an animal.展开更多
基金Supported in part by the Bruggeman Medical Foundation
文摘AIM： To investigate the role of small intestinal carcinoid tumor-derived fibrotic mediators, TGFβ1 and CTGF, in the mediation of fibrosis via activation of an ＂intestinal＂ stellate cell. METHODS： GI carcinoid tumors were collected for Q RT-PCR analysis of CTGF and TGFβ1. Markers of stellate cell desmoplasia were identified in peritoneal fibrosis by immunohistochemistry and stellate cells cultured from fresh resected fibrotic tissue. CTGF and TGFβ1 were evaluated using quantitative tissue array profiling （AQUA analysis） in a GI carcinoid tissue microarray （TMA） with immunostaining and correlated with clinical and histologically documented fibrosis. Serum CTGF was analyzed using a sandwich ELISA assay. RESULTS： Message levels of both CTGF and TGFβ1 in SI carcinoid tumors were significantly increased （〉 2-fold, P 〈 0.05） versus normal mucosa and gastric （non-fibrotic） carcinoids. Activated stellate cells and markers of stellate cell-mediated fibrosis （vimentin, desmin） were identified in histological fibrosis. An intestinal stellate cell was immunocytochemically and biochemically characterized and its TGFβ1 （10-7M） initiated CTGF transcription response （〉 3-fold, P 〈 0.05） demonstrated. In SI carcinoid tumor patients with documented fibrosis, TMA analysis demonstrated higher CTGF immunostaining （AQUA Score： 92 ± 8, P 〈0.05）, as well as elevated TGFβ1 （90.6 ± 4.4, P 〈 0.05）. Plasma CTGF （normal 12.5 ± 2.6 ng/mL） was increased in SI carcinoid tumor patients （31 ± 10 ng/mL, P 〈 0.05） compared to non-fibrotic GI carcinoids （〈 15 ng/mL） CONCLUSION： SI carcinoid tumor fibrosis is a CTGF/ TGFβl-mediated stellate cell-driven fibrotic response. The delineation of the biology of fibrosis will facilitate diagnosis and enable development of agents to obviate its local and systemic complications.
基金supported by a grant from the Natural Science Foundation of Hubei Province(No.2010CHB00401)
文摘Summary： The activation of hepatic stellate cells （HSCs） and their transformation to myofibroblasts are the key steps in the pathological progress of liver fibrosis. The transforming growth factor-J3 （TGFβ）/Smad pathway is involved in the proliferation and collagen synthesis of HSCs. This study aimed to examine the effect of the protease inhibitor MG132 on the signaling pathway of TGFβ/Smad in HSC-T6 cells and seek a novel therapeutic approach for liver fibrosis. The HSC-T6 cells were treated with MG132 at different concentrations （0-10 maol/L）. Cell proliferation was detected by MTT method. The mRNA and protein expression levels of TGFI31, Smad3 and Smad7 were determined in HSC-T6 cells by real-time PCR and Western blotting, respectively, after treatment with MG132 at different con- centrations （1, 2, 3 μtmol/L） or RPMI1640 alone （serving as control）. The results showed that MG132 could inhibit the proliferation of HSC-T6 cells in a dose-dependent manner, and the IC50 of MG132 was 6.84 μmol/L. After treatment with MG132 at 1, 2 or 3 nol/L for 24 h, the mRNA expression levels of TGF-β1 and Smad3 were significantly decreased （P〈0.05）, but the Smad7 mRNA expression had no significant change （P〉0.05）. There was also a significant decrease in the protein expression level of TGF-β1 and Smad3 （P〈0.05）. However, the expression of Smad7 protein was substantially increased when compared with the control group （P〈0.05）. It was concluded that the inhibition of TGFi/Smad pathway in HSC-T6 cells by MG132 can reduce the production of profibrosis factors （TGFI31, Smad3） and promote the expression of anti-fibrosis factor （Smad7）, suggesting that MG132 may become a po- tential therapeutic alternative for liver fibrosis.
文摘We often eat more than our body needs. We live in an environment where high calorie food is abundant and physical activities are limited. Living in this environment, maintaining healthy bodyweight becomes challenging and obesity becomes a social burden. Why do we continue to eat even after the metabolic needs are satisfied？ Feeding is an ancient behavior essential to survive. Thus the mechanisms to regulate appetite, energy expenditure, and energy storage are well conserved throughout animals. Based on this conservation, we study why we fail to control appetite using a simple genetic model system C. elegans. We have discovered certain genetic components that when misregulated have animals eat more and store more fat. In this review we discuss how these genes work in the appetite control circuit to ultimately understand overall appetite control behavior. We will also briefly discuss how social influence affects feeding regardless of the metabolic status of an animal.
