• Title/Summary/Keyword: Smads

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Protective Effects of Prunella Vulgaris on Glomerular Injury in Streptozotocin-Induced Diabetic Rats (하고초 추출물의 streptozotocin 유발 당뇨 랫트 사구체 손상 개선 효과)

  • Yoon, Jung Joo;Park, Ji Hun;Jeong, Da Hye;Han, Byung Hyuk;Choi, Eun Sik;Lee, Yun Jung;Kang, Dae Gill;Lee, Ho Sub
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.31 no.5
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    • pp.264-269
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    • 2017
  • Prunella vulgaris, well-known traditional medicinal plant, is used for the cure of abscess, scrofula, hypertension and urinary diseases. Diabetic nephropathy is the most common cause of end-stage renal disease. The pathological characteristics of diabetic nephropathy are glomerular and tubular basement membrane thickening. The aim of the present study was to evaluate the effect of Prunella vulgaris, on diabetic glomerular injury in streptozotocin-induced diabetes rats. Diabetes mellitus was induced by a single intraperitoneal injection of streptozotocin (STZ; 45 mg/kg) and confirmed by random glucose level higher than ${\leq}300mg/dL$. The experimental rats were divided into five groups: control group (Male SD rats), STZ group (Male SD rats injected STZ), Aminoguanidine group (Male SD rats injected STZ + AG 100 mg/kg/day), Low dose group (Male SD rats injected STZ + APV 100 mg/kg/day), High dose group (Male SD rats injected STZ + APV 300 mg/kg/day). AG or APVs were administered once a day for 8 weeks. Body weight and food/water intake were measured every four weeks. At the end of study, the kidneys were collected and cut into pieces for immunohistochemistry and western blot analysis. Our study showed that body weight and water/food intake were no significant differences between untreated STZ-induced diabetic rat and APV treated-STZ rat. However, phosphorylation of receptor-regulated Smads (Smad3) was significantly decreased in APV treated-STZ rat as compared with the diabetic group. In addition, APV was improved nephrin level in kidney tissue. Therefore, we suggest that APV has a protective effect against STZ-induced diabetic glomerular injury.

20(S)-ginsenoside Rg3 exerts anti-fibrotic effect after myocardial infarction by alleviation of fibroblasts proliferation and collagen deposition through TGFBR1 signaling pathways

  • Honglin Xu;Haifeng Miao;Guanghong Chen;Guoyong Zhang;Yue Hua;Yuting Wu;Tong Xu;Xin Han;Changlei Hu;Mingjie Pang;Leyi Tan;Bin Liu;Yingchun Zhou
    • Journal of Ginseng Research
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    • v.47 no.6
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    • pp.743-754
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    • 2023
  • Background: Myocardial fibrosis post-myocardial infarction (MI) can induce maladaptive cardiac remodeling as well as heart failure. Although 20(S)-ginsenoside Rg3 (Rg3) has been applied to cardiovascular diseases, its efficacy and specific molecular mechanism in myocardial fibrosis are largely unknown. Herein, we aimed to explore whether TGFBR1 signaling was involved in Rg3's anti-fibrotic effect post-MI. Methods: Left anterior descending (LAD) coronary artery ligation-induced MI mice and TGF-β1-stimulated primary cardiac fibroblasts (CFs) were adopted. Echocardiography, hematoxlin-eosin and Masson staining, Western-blot and immunohistochemistry, CCK8 and Edu were used to study the effects of Rg3 on myocardial fibrosis and TGFBR1 signaling. The combination mechanism of Rg3 and TGFBR1 was explored by surface plasmon resonance imaging (SPRi). Moreover, myocardial Tgfbr1-deficient mice and TGFBR1 adenovirus were adopted to confirm the pharmacological mechanism of Rg3. Results: In vivo experiments, Rg3 ameliorated myocardial fibrosis and hypertrophy and enhanced cardiac function. Rg3-TGFBR1 had the 1.78×10-7 M equilibrium dissociation constant based on SPRi analysis, and Rg3 inhibited the activation of TGFBR1/Smads signaling dose-dependently. Cardiac-specific Tgfbr1 knockdown abolished Rg3's protection against myocardial fibrosis post-MI. In addition, Rg3 downregulated the TGF-β1-mediated CFs growth together with collagen production in vitro through TGFBR1 signaling. Moreover, TGFBR1 adenovirus partially blocked the inhibitory effect of Rg3. Conclusion: Rg3 improves myocardial fibrosis and cardiac function through suppressing CFs proliferation along with collagen deposition by inactivation of TGFBR1 pathway.

THE EFFECT OF BMP REGULATED SMAD PROTEIN ON ALKALINE PHOSPHATASE GENE EXPRESSION (Smad에 의한 alkaline phosphatase 유전자의 발현 조절기전)

  • Kim, Nan-Jin;Ryoo, Hyun-Mo;Kim, Hyun-Jung;Kim, Young-Jin;Nam, Soon-Hyeun
    • Journal of the korean academy of Pediatric Dentistry
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    • v.28 no.2
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    • pp.238-246
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    • 2001
  • Bone morphogenetic proteins(BMPs), members of the transforming growth factor $\beta$(TGF-$\beta$) superfamily were first identified as the factors that induce ectopic bone formation in vivo, when implanted into muscular tissue. Especially BMP-2 inhibits terminal differentiation of C2C12 myoblasts and converts them into osteoblast lineage cells. In the molecular mechanism of the signal transduction of TGF-$\beta$ and related factors, intracellular signaling proteins were identified as Smad. In previous study, it has been reported that Smad 1 and Smad 5, which belong to the R-Smad family mediate BMP signaling, were involved in the induction of osteoblast differentiation in C2C12 cells. To understnad the role of Smads involved in osteogenic transdifferentiation in C2C12 cell, in present study, after we stably transfected C2C12 cells with each. Smad(Smad 1,Smad 5) expression vector, cultured for 3 days and stained for alkaline phophatase activity. ALP activity positive cells appeared in the Smad 1, Smad 5 stably transfected cell even in the abscence of BMP. After transiently co-transfected C2C12 cells with each Smad expression vector and ALP promoter, it was examined that Smad 1 and Smad 5 expression vector had increased about 2 fold ALP promoter activity in the abscence of BMP. These result suggested that both Smad 1 and Smad 5 were involved in the intracellular BMP signals which induce osteoblast differentiation in C2C12 cells. The effect of BMP on C2C12 cells with Smad 1, Smad 5 transfected were studied by using northern blot analysis. the treatment of BMP upregulated ALP mRNA level in three groups, especially upregulation of ALP was larger in Smad 1, Smad 5 transfected cell than control group. Pretreatment with cycloheximide($10{\mu}g/ml$), a protein synthesis inhibitor resulted in blocking the ALP gene expression even in BMP(100ng/ml) treated cell. These results suggested that Smad increased the level of ALP mRNA via the synthesis of a certain transcriptional regulatory protein.

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