scholarly journals Dendrobium Mixture Ameliorates Diabetic Nephropathy in db/db Mice by Regulating the TGF-β1/Smads Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yong Chen ◽  
Xiaohui Lin ◽  
Yanfang Zheng ◽  
Wenzhen Yu ◽  
Fan Lin ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Lipid Level ◽  
Fasting Blood Glucose ◽  
Blood Lipid ◽  
Control Group ◽  
Expression Levels ◽  
Tgf Β1

Dendrobium mixture (DMix) is an effective treatment for diabetic nephropathy (DN), but the molecular mechanism underlying its action remains unclear. In this study, we investigated whether DMix regulates the transforming growth factor-β1 (TGF-β1)/Smads signal transduction pathway. Twenty-four db/db mice were randomly divided into three groups: the model, DMix, and gliquidone groups, while eight db/m mice were selected as the normal control group. The drug was administered by continuous gavage for 8 weeks. Body weight (BW), kidney weight (KW), kidney index, fasting blood glucose (FBG), blood lipid, 24-hour urinary albumin excretion rate, blood urea nitrogen, and serum creatinine levels were measured. Pathological changes in the renal tissue were observed under a light microscope. Real-time quantitative PCR and immunohistochemical staining were used to detect the mRNA and protein expression levels of TGF-β1 and alpha-smooth muscle actin (α-SMA), respectively, in renal tissues. TGF-β1, Smad2, p-Smad2, Smad3, p-Smad3, and α-SMA expression levels were measured using western blotting. The results showed that DMix significantly reduced the FBG level, BW, KW, and blood lipid level and improved renal function in db/db mice. Histopathology showed that DMix alleviated glomerular mesangial cell proliferation and renal interstitial fibrosis in db/db mice. Additionally, DMix reduced the protein and mRNA expression levels of TGF-β1 and α-SMA and inhibited Smad2 and Smad3 phosphorylation. We conclude that DMix may inhibit renal fibrosis and delay the progression of DN by regulating the TGF-β1/Smads signaling pathway.

scholarly journals Dendrobium Mixture Improved Diabetic Nephropathy in db/db Mice by Regulating TGF-β1/Smads Signal Transduction

2021 ◽  
Author(s):  
Yong Chen ◽  
Xiaohui Lin ◽  
Yanfang Zheng ◽  
Wenzhen Yu ◽  
Fan Lin ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Diabetic Nephropathy ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Fasting Blood Glucose ◽  
Blood Lipid ◽  
Control Group ◽  
Tgf Β1

Abstract BackgroundDendrobium mixture (DMix) is an effective treatment for diabetic nephropathy (DN), but the underlying molecular mechanism remains unclear. In this study, we investigated whether DMix regulates the transforming growth factor-β1 (TGF-β1)/Smads signal transduction pathway. MethodsTwenty-four db/db mice were randomly divided into three groups: the model, DMix, and gliquidone groups, while eight db/m mice were selected as the normal control group. The drug was administered by continuous gavage for 8 weeks. Body weight (BW), kidney weight (KW), kidney index, fasting blood glucose (FBG), blood lipid, 24-hour urinary albumin excretion rate, blood urea nitrogen, and serum creatinine levels were measured. Pathological changes in the renal tissue were observed using a light microscope. Real-time quantitative PCR and immunohistochemical staining were used to detect mRNA expression of TGF-β1 and alpha-smooth muscle actin (α-SMA) genes and proteins, respectively, in renal tissues. TGF-β1, Smad2, p-Smad2, Smad3, p-Smad3, and α-SMA expression levels were measured using western blotting. ResultsDMix significantly reduced FBG level, BW, KW, and blood lipid level, and improved renal function in db/db mice. Histopathology showed that DMix alleviated glomerular mesangial cell proliferation and renal interstitial fibrosis in db/db mice. Additionally, DMix reduced protein and mRNA expression of TGF-β1 and α-SMA, and inhibited Smad2 and Smad3 phosphorylation. ConclusionsThe findings suggest that DMix may inhibit renal fibrosis and delay the progression of DN by regulating the TGF-β1/Smads signaling pathway. Key words: Diabetic nephropathy, Dendrobium mixture, TGF-β1/Smads signaling pathway

scholarly journals Sulodexide Prevents Peritoneal Fibrosis by Downregulating the Expression of TGF-β1 and Its Signaling Pathway Molecules

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Zhiqiang Duan ◽  
Jia Yao ◽  
Nan Duan ◽  
Min Wang ◽  
Shiwei Wang
Keyword(s):  
Peritoneal Dialysis ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Vascular Endothelial Cells ◽  
Inflammatory Factors ◽  
Control Group ◽  
Peritoneal Fibrosis ◽  
Blank Control Group ◽  
Peritoneal Tissue ◽  
Tgf Β1

Peritoneal dialysis is one of the main renal replacement treatments. However, long-term peritoneal dialysis keeps the peritoneum in contact with the sugar-containing nonphysiological peritoneal fluid, which leads to recurrent peritonitis, peritoneal fibrosis, and failure of ultrafiltration. Transforming growth factor-β1 (TGF-β1), related cytokines, and inflammatory factors are closely related to peritoneal fibrosis. Sulodexide (SLX) is a new type of glycosaminoglycan preparation, which is involved in the formation of an anionic charge barrier and can maintain the selective permeability of vascular endothelial cells. In this study, the innovative analysis of SLX specifically prevents the process of peritoneal dialysis peritoneal fibrosis by downregulating the expression of TGF-β1 and its signaling pathway molecules. We randomly divided 30 rats into three groups. The blank control group received no treatment. The peritoneal dialysis model group was injected with 4.25% peritoneal dialysate (PDF) 20 ml daily, and the SLX group was injected with 4.25% PDF 20 ml + sulodexide (SLX) 20 mg/kg daily. After 8 weeks of dialysis, the rats were sacrificed, and the peritoneal function test was performed to determine the amount of glucose transport and ultrafiltration. The thickness of peritoneal per unit area was observed under high magnification. The level of inflammation in peritoneal tissue and the expression of TGF-β1/Smad were detected. The results showed that SLX can significantly improve peritoneal tissue thickening and inflammation, can downregulate the expression of TGF-β1, Smad2, Smad3, and Smad7 in peritoneal tissue, and improve the progression of peritoneal fibrosis.

Fibrogenic cytokine levels in bronchoalveolar lavage aspirates 15 years after exposure to sulfur mustard

2004 ◽  
Vol 287 (6) ◽  
pp. L1160-L1164 ◽  
Author(s):  
Reza Aghanouri ◽  
Mostafa Ghanei ◽  
Jafar Aslani ◽  
Hossein Keivani-Amine ◽  
Ferdos Rastegar ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Transforming Growth Factor ◽  
Sulfur Mustard ◽  
Interstitial Fibrosis ◽  
Control Group ◽  
Case Group ◽  
War Veterans ◽  
Test Kit ◽  
And Control ◽  
Tgf Β1

Over 100,000 Iranian war veterans suffer from chronic effects of mustard gas exposure. Sulfur mustard was used by Iraq during the Iraqi-imposed war on Iran (between 1980 and 1988). The major complaints of these patients are mild interstitial fibrosis and bronchiolitis. We aimed to determine the state of fibrosis progression and assessed transforming growth factor (TGF)-β1 levels in pulmonary samples and in bronchoalveolar lavage (BAL) aspirates. A total of 126 war veterans confirmed for lung disease were assessed and compared with three control groups: 1) 64 veterans not exposed to chemical agents, 2) 12 idiopathic pulmonary fibrosis civilian patients, and 3) 33 normal persons. BAL was performed via a flexible fiber-optic bronchoscope and the standard manual method. Total protein was measured by Bradford assay, and samples were corrected with regard to coefficients. Samples were concentrated 15-fold by lyophilization and resolubilization. Samples were double-checked using an ELISA test kit. The Mann-Whitney test was used for the data analysis using commercial software. We detected that significant differences between TGF-β1 levels between the case group and control group 1 ( P = 0.001) and control group 3 ( P = 0.003). No significant differences were found between the case group and control group 2 ( P = 0.57). Inflammation and fibrotic processes in lung tissue of patients exposed to sulfur mustard may be progressive so IFN-γ may be a useful drug to these patients' treatment.

scholarly journals Nephroprotective effect of losartan in IgA model rat

2019 ◽  
Vol 47 (10) ◽  
pp. 5205-5215
Author(s):  
Li Xing ◽  
Er Lin Song ◽  
Xi Bei Jia ◽  
Jing Ma ◽  
Bing Li ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Smooth Muscle Actin ◽  
Control Group ◽  
Model Group ◽  
Sprague Dawley ◽  
Tubulointerstitial Injury ◽  
Expression Levels ◽  
Losartan Group ◽  
Tgf Β1

Objective This study was performed to investigate the possible nephroprotective effects of losartan in a rat model of experimental IgA nephropathy (IgAN). Methods Thirty male Sprague–Dawley rats were randomly divided into three groups. The rats in the model group were treated with bovine serum albumin (oral gavage), lipopolysaccharide (tail vein injection), and carbon tetrachloride (subcutaneous injection); rats in the losartan group received treatments similar to those of the model group, and were orally gavaged with losartan; and rats in the control group received phosphate-buffered saline alone (both orally and intravenously). Results Losartan treatment lowered the 24-hour urinary protein, serum blood urea nitrogen, and serum creatinine levels. Proliferating mesangial cells with a variable increase in the mesangial matrix were detected in the model group, whereas injury in the losartan group was significantly attenuated. Immunohistochemistry revealed that the expression levels of transforming growth factor (TGF)-β1 and α-smooth muscle actin were significantly elevated in the model group but reduced in the losartan group. The expression levels of TGF-β1 and monocyte chemoattractant protein-1 were minimal in the control group, significantly increased in the model group, and reduced in the losartan group. Conclusion Losartan has a protective effect against tubulointerstitial injury in IgAN.

scholarly journals MicroRNA-485 Modulates the TGF-β/ Smads Signaling Pathway in Chronic Asthmatic Mice by Targeting Smurf2

2018 ◽  
Vol 51 (2) ◽  
pp. 692-710 ◽  
Author(s):  
Jing Wang ◽  
Hong-Yan Li ◽  
Hu-Shan Wang ◽  
Zhen-Bo  Su
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Quantitative Polymerase Chain Reaction ◽  
Transforming Growth Factor Β ◽  
Airway Smooth Muscle Cell ◽  
Cell Cycle Distribution ◽  
Chronic Asthma ◽  
Expression Levels ◽  
Tgf Β1

Background/Aims: Chronic respiratory conditions continue to plague millions of people worldwide. We aimed to elucidate the detailed mechanisms of microRNA-485 (miR-485) in airway smooth muscle cell (ASMC) proliferation and apoptosis in chronic asthmatic mice. Methods: A mouse model of chronic asthma was established. Ovalbumin was used to induce chronic asthma in the mice. The levels of transforming growth factor β (TGF-β), interleukin (IL)-4, IL-5, IL-13 and IL-17 in bronchoalveolar lavage fluid in mice were measured by enzyme-linked immunoassays (ELISAs). ASMCs were transfected with miR-485 mimic, miR-485 inhibitor and siRNA-Smurf2. The reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analyses were applied to detect the mRNA and protein levels of Smurf2, α-SMA, TGF-β1 and decapentaplegic homolog (Smads). The MTT assay was utilized for cell proliferation, while flow cytometry was conducted to assess cell cycle distribution and apoptosis. Results: Lower expression of miR-485 and higher expression levels of TGF-β1, IL-4, IL-5, IL-13 and IL-17 were detected in mice with chronic asthma. Smurf2 was identified as the target gene of miR-485. Upregulation of miR-485 mimic and downregulation of Smurf2 decreased expression levels of Smurf2, α-SMA, TGF-β1 and Smad3, inhibited cell proliferation and increased apoptosis, while contrary results were observed in ASMCs transfected with miR-485 inhibitor. Conclusion: Overexpressed miR-485 inhibits cell proliferation and promotes apoptosis of ASMCs through the Smurf2-mediated TGF-β/Smads signaling pathway in mice with chronic asthma.

scholarly journals Glycyrrhetinic acid alleviates radiation-induced lung injury in mice

2017 ◽  
Vol 58 (1) ◽  
pp. 41-47 ◽  
Author(s):  
Jinmei Chen ◽  
Weijian Zhang ◽  
Lurong Zhang ◽  
Jiemin Zhang ◽  
Xiuying Chen ◽  
...  
Keyword(s):  
Lung Injury ◽  
Signaling Pathway ◽  
Lung Tissue ◽  
Transforming Growth Factor ◽  
Early Stage ◽  
Glycyrrhetinic Acid ◽  
Control Group ◽  
X Rays ◽  
Radiation Induced ◽  
Tgf Β1

Abstract Radiation-induced lung injury (RILI) is a common complication of thoracic radiotherapy, but efficacious therapy for RILI is lacking. This study ascertained whether glycyrrhetinic acid (GA; a functional hydrolyzed product of glycyrrhizic acid, which is extracted from herb licorice) can protect against RILI and investigated its relationship to the transforming growth factor (TGF)-β1/Smads signaling pathway. C57BL/6 mice were divided into four groups: a control group, a GA group and two irradiation (IR) groups. IR groups were exposed to a single fraction of X-rays (12 Gy) to the thorax and administered normal saline (IR + NS group) or GA (IR + GA group). Two days and 17 days after irradiation, histologic analyses were performed to assess the degree of lung injury, and the expression of TGF-β1, Smad2, Smad3 and Smad7 was recorded. GA administration mitigated the histologic changes of lung injury 2 days and 17 days after irradiation. Protein and mRNA expression of TGF-β1, Smad2 and Smad3, and the mRNA level of Smad7, in lung tissue were significantly elevated after irradiation. GA decreased expression of TGF-β1, Smad2 and Smad3 in lung tissue, but did not increase Smad7 expression. GA can protect against early-stage RILI. This protective effect may be associated with inhibition of the TGF-β1/Smads signaling pathway.

scholarly journals Nocardia rubra cell wall skeleton accelerates cutaneous wound healing by enhancing macrophage activation and angiogenesis

2018 ◽  
Vol 46 (6) ◽  
pp. 2398-2409 ◽  
Author(s):  
Yi Wang ◽  
Ying Hu ◽  
Ben Ma ◽  
Fei Wang ◽  
Sheng Liu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Wall ◽  
Transforming Growth Factor ◽  
Wound Dressings ◽  
Control Group ◽  
Cutaneous Wound Healing ◽  
Full Thickness ◽  
Cutaneous Wound ◽  
Expression Levels ◽  
Tgf Β1

Objective This study was performed to investigate the effect of Nocardia rubra cell wall skeleton (N-CWS) on wound healing of full-thickness skin defects. Methods Two 2- × 2-cm full-thickness wounds, one on each side of the midline, were made on the back of 12 rats. One wound was covered with Vaseline gauze soaked in normal saline, whereas the other was covered with Vaseline gauze and N-CWS. Wound dressings were changed every other day from day 0 (wound creation) to day 11. Four of the 12 rats were killed on day 7, and biopsy samples were obtained for biochemical and histopathological analyses. The expression levels of CD31, CD68, and F4/80 in the tissues were examined immunohistologically. The expression of transforming growth factor (TGF)-β1 in the wound was determined by western blot. Results N-CWS increased the wound healing rate, reduced the complete wound healing time, and increased the expression levels of CD31, CD68, and F4/80 on day 7. The TGF-β1 expression level in the wound was significantly higher in the N-CWS group than in the control group on day 7. Conclusions N-CWS can activate macrophages, increase TGF-β1 expression, and enhance angiogenesis and thus accelerate cutaneous wound healing.

scholarly journals Astragaloside IV attenuated TGF-β1- induced epithelial-mesenchymal transition of renal tubular epithelial cells via connexin43 and Akt/mTOR signaling pathway

2021 ◽  
Author(s):  
Yonghong Lian ◽  
Cuiqiong Li ◽  
Jianchun Li ◽  
Yongxiang Xie ◽  
Qiancheng Liu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Interstitial Fibrosis ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Renal Interstitial Fibrosis ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Protein Expressions ◽  
Tgf Β1 ◽  
Different Doses

Abstract INTRODUCTION: The objective of the study was to observe whether Cx43 could regulate EMT of RTECs by influencing Akt/mTOR signaling pathway, and whether ASV could inhibit the development of renal interstitial fibrosis by regulating Cx43. METHODS: Lentivirus infection was transfected into RTECs with the final concentration of 50×PFU/ cell to regulate the expression of Cx43.And RTECs were intervened by different doses of ASV. After synchronous culture of RTECs in each group,cell morphological changes were observed and the expression levels of EMT-related indicators, and the expression levels of Cx43, the protein expressions and phosphorylation levels AKT and mTOR in different groups were detected by WB. RESULTS: When the expression of Cx43 in RTECs was regulated by lentivirus infection, the degree of EMT induced by TGF‑β1 and the phosphorylation level of Akt and mTOR were changed accordingly, indicating that Akt/mTOR pathway might be a downstream molecular mechanism by which Cx43 could regulate EMT. After intervention with different doses of ASV, the expression level of Cx43 increased with obvious concentration dependence, and the expression levels of p-Akt and p- mTOR were significantly altered, suggesting that ASV could effectively increase the protein expressions of TGF‑β1-induced Cx43 in RTECs and inhibit the phosphorylation levels of Akt and mTOR. CONCLUSION: Cx43 is the main material basis of RTECs’injury, and ASV could inhibit TGF-β1 induced RTECs transdifferentiation. In-depth study of the mechanism may provide a broad application prospect for the treatment of renal interstitial fibrosis.

scholarly journals Protective Effects of Chromium Picolinate Against Diabetic-Induced Renal Dysfunction and Renal Fibrosis in Streptozotocin-Induced Diabetic Rats

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 398 ◽  
Author(s):  
Shan Shan Qi ◽  
Hong Xing Zheng ◽  
Hai Jiang ◽  
Li Ping Yuan ◽  
Le Chen Dong
Keyword(s):  
Diabetic Nephropathy ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Biological Activities ◽  
Serum Insulin ◽  
Treated Group ◽  
Chromium Picolinate ◽  
Glomerular Sclerosis ◽  
Protective Effects ◽  
Tgf Β1

Diabetic nephropathy (DN) is one of the most important complications of diabetes, and the leading cause of end-stage renal disease (ESRD). While Chromium picolinate (CrPic) supplementation has been found to be effective in treating diabetes, its effects on diabetic-induced nephropathy have not been studied. Therefore, in this study, CrPic (1 mg kg−1 d−1) was administered to a DN rat model by oral gavage for eight weeks to investigate its effects. The results show that CrPic supplementation caused a decrease in levels of blood glucose, serum insulin, blood urea nitrogen (BUN), serum creatinine, and urinary albumin in DN rats. It also reversed renal pathological changes, including renal glomerular sclerosis and interstitial fibrosis. In addition, the oxidative defense system in the kidneys of DN rats was found to be improved; the biological activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) increased; and the content of malondialdehyde (MDA) lowered. Immunohistochemical results reveal that the expression levels of renal transforming growth factor-β1 (TGF-β1), Smad 2, and Smad 3 decreased significantly in the kidneys of rats in the CrPic-treated group. CrPic administration was thus found to ameliorate diabetic nephropathy in SD rats via an antioxidative stress mechanism, as well the ability to inhibit TGF-β1/Smad2/3 expression. This study suggests that CrPic could be a potential renal-protective nutrient against diabetic nephropathy.

scholarly journals Thyroid hormone ameliorates diabetic nephropathy in a mouse model of type II diabetes

2011 ◽  
Vol 209 (2) ◽  
pp. 185-191 ◽  
Author(s):  
Yi Lin ◽  
Zhongjie Sun
Keyword(s):  
Diabetic Nephropathy ◽  
Type Ii Diabetes ◽  
Structural Damage ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Diabetic Patients ◽  
Type Ii ◽  
Simultaneous Treatment ◽  
Pi3k Activity ◽  
Tgf Β1

Conventional therapies for diabetic patients, such as strict glycemic control, do not completely stop the progression of diabetic nephropathy. Serum-free tri-iodothyronine (T3) levels were lower in patients with type II diabetes. The purpose of this study was to test a hypothesis that treatment with T3 would improve diabetic nephropathy in db/db mice, a model of type II diabetes. Male db/db mice (16 weeks) were treated with T3 for 4 weeks. Urinary excretions of albumin and blood glucose levels were measured. Kidneys were collected for histological examination and molecular assays of transforming growth factor-β1 (TGF-β1) expression and phosphatidylinositol 3-kinase (PI3K). T3 attenuated albuminuria in db/db mice, suggesting an improved kidney function. T3 significantly decreased accumulation of collagenous components in cortical interstitium (interstitial fibrosis) and expansion of mesangial matrix in glomeruli (glomerulosclerosis) and prevented the loss of glomeruli in db/db mice. Therefore, T3 improved the renal structural damage seen in diabetic mice. Notably, diabetic nephropathy was accompanied by a significant decrease in PI3K activity and an increase in TGF-β1 expression in kidneys. T3 restored renal PI3K activity, attenuated hyperglycemia, and decreased renal TGF-β1 expression in db/db mice. These effects of T3 were abolished by simultaneous treatment with PI3K inhibitor (LY294002). These data suggest that T3 prevented progressive kidney damage and remodeling in db/db mice by improving insulin signaling (e.g. PI3K activity).

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