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 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 Quantification of TGF-β1 mRNA along rat nephron in obstructive nephropathy

2001 ◽  
Vol 281 (3) ◽  
pp. F513-F521 ◽  
Author(s):  
Kyoichi Fukuda ◽  
Koji Yoshitomi ◽  
Taihei Yanagida ◽  
Masanori Tokumoto ◽  
Hideki Hirakata
Keyword(s):  
In Situ Hybridization ◽  
Mrna Expression ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Proximal Tubules ◽  
Obstructive Nephropathy ◽  
Renal Tubules ◽  
Rt Pcr ◽  
Tgf Β1

Unilateral ureteral obstruction (UUO) leads to interstitial fibrosis of the obstructed kidney, and transforming growth factor-β1 (TGF-β1) is thought to play an important role in this process. Although increased TGF-β1 mRNA expression in the obstructed kidney has been demonstrated, the source of the increased TGF-β1 remains to be elucidated. To determine the precise localization of TGF-β1 in the obstructed kidney, we examined TGF-β1 mRNA expression using in situ hybridization and competitive RT-PCR in rats with UUO. In situ hybridization demonstrated that TGF-β1 mRNA expression was preferentially increased in tubular epithelial cells and to a lesser degree in infiltrating macrophages in obstructed kidneys. Quantitative analysis using competitive RT-PCR in microdissected nephron segments revealed that levels of TGF-β1 mRNA in obstructed kidneys relative to control kidneys increased significantly in proximal tubules, thick ascending limbs of Henle, and distal convoluted tubules, whereas those in glomeruli and collecting ducts did not change significantly. Of the tubular segments, the proximal tubules appeared to predominantly contribute to increased TGF-β1 mRNA. Our findings suggest that renal tubules, particularly proximal tubules, are the main contributors to increased TGF-β1 mRNA expression in obstructed kidneys and to the subsequent interstitial fibrosis.

Effects of danshensu on the transforming growth factor-β1/smads signaling pathway in rats with lung injury

2020 ◽  
Vol 10 (11) ◽  
pp. 1816-1823
Author(s):  
Jing Qin ◽  
Xiaoqiang Zhang ◽  
Shengyan Wang ◽  
Yongming Zhang
Keyword(s):  
Lung Injury ◽  
Mrna Expression ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Abdominal Cavity ◽  
Physiological Saline ◽  
Transforming Growth Factor Β1 ◽  
Control Group ◽  
Sprague Dawley ◽  
Sd Rats

Observe the therapeutic effect of Danshensu on lung injury for rats, as well as explore the mechanism of Danshensu in TGF-β1/Smads signaling. Thirty Sprague-Dawley (SD) rats were intratracheally instilled with bleomycin to induce lung injury and interstitial fibrosis. Divided Thirty rats into three groups. DA group (η = 10): Inject 15 mg/kg Danshensu into the abdominal cavity; DXM group (η = 10): Inject 1 mg/kg dexamethasone into the abdominal cavity; BLM group (η = 10): Inject 2 mL physiological saline into the abdominal cavity. Then ten SD rats were intratracheally instilled with physiological saline as normal control group, NC group: Inject 2 mL physiological saline into the abdominal cavity. After a period of 28 days, the degree of pulmonary alveolitis was evaluated using hematoxylin-eosin (HE) staining, and the degree of lung fibrosis was evaluated using Masson?s trichrome (MT) staining. The immunohistochemistry was used to determine the expression of α-SMA. Magnetic nanoparticles+rtQ-PCR was used to determine the mRNA expressions for TGF-β1, Smad3, and Smad7. The alveolitis and pulmonary fibrosis in DA rats were obviously less than those in BLM rats and DXM rats. The expression of α-SMA in DA rats was obviously less than that of in BLM rats and DXM rats; the mRNA expression of TGF-β1 and Smad3 in DA rats were obviously reduced; the Smad7 mRNA expression was obviously up-regulated. DA can alleviate rat lung injury caused by bleomycin. Inhibiting the TGF-β1 and Smad3 mRNA expression, as well as boosting the Smad7 mRNA expression is one of the mechanisms by which Danshensu reduces lung injury.

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 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 Expression of Transforming Growth Factor Beta Isoforms in Canine Endometrium with Cystic Endometrial Hyperplasia–Pyometra Complex

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1844
Author(s):  
Marta Rybska ◽  
Magdalena Woźna-Wysocka ◽  
Barbara Wąsowska ◽  
Marek Skrzypski ◽  
Magdalena Kubiak ◽  
...  
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Transforming Growth Factor Beta ◽  
Endometrial Hyperplasia ◽  
Transforming Growth Factor ◽  
Control Group ◽  
Key Factor ◽  
Growth Factor Beta ◽  
Uterine Diseases ◽  
Tgf Β1

Cystic endometrial hyperplasia (CEH) and pyometra are the most frequently diagnosed uterine diseases affecting bitches of different ages. Transforming growth factor beta (TGF-β) has been classified in females as a potential regulator of many endometrial changes during the estrous cycle or may be involved in pathological disorders. The aim of this study was to determine the expression of TGF-β1, -β2 and -β3 in the endometrium of bitches suffering from CEH or a CEH–pyometra complex compared to clinically healthy females (control group; CG). A significantly increased level of TGF-β1 mRNA expression was observed in the endometrium with CEH–pyometra compared to CEH and CG. Protein production of TGF-β1 was identified only in the endometrium of bitches with CEH–pyometra. An increase in TGF-β3 mRNA expression was observed in all the studied groups compared to CG. The expression of TGF-β2 mRNA was significantly higher in CEH and lower in CEH–pyometra uteri. The results indicate the presence of TGF-β cytokines in canine endometrial tissues affected by proliferative and degenerative changes. However, among all TGF-β isoforms, TGF-β1 could potentially be a key factor involved in the regulation of the endometrium in bitches with CEH–pyometra complex.

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).

scholarly journals Effect of Huayu Tongluo Herbs on Reduction of Proteinuria via Inhibition of Wnt/β-Catenin Signaling Pathway in Diabetic Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Lu Bai ◽  
Beibei Huo ◽  
Zhiqiang Chen ◽  
Qian Guo ◽  
Jing Xu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Interstitial Fibrosis ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Control Group ◽  
Intragastric Administration ◽  
Beta Catenin ◽  
Protein Excretion

The study investigated the expression of Wnt/β-catenin pathway in diabetic rats and the intervention effect of Huayu Tongluo herbs (HTH). Ten rats were randomly selected as control group and the remaining rats were established as diabetic models. The diabetic rats were randomly divided into model group and HTH treatment group. The intervention was intragastric administration in all rats for 20 weeks. At the end of every 4 weeks, fasting blood glucose and 24 h urinary total protein quantitatively were measured. At the end of the 20th week, biochemical parameters and body weight were tested. The kidney tissues were observed under light microscope and transmission electron microscopy. We examined Wnt/beta-catenin signaling pathway key proteins and renal interstitial fibrosis related molecular markers expression. The results showed that HTH could reduce urinary protein excretion and relieve renal pathological damage. Wnt4, p-GSK3β (S9), and β-catenin expression were decreased in the signaling pathway, but GSK3β level was not changed by HTH in diabetic rats. Furthermore, the expressions of TGF-β1 and ILK were decreased, but the level of E-cadherin was increased in diabetic rats after treatment with HTH. This study demonstrated that HTH could inhibit the high expression of Wnt/β-catenin pathway in kidney of diabetic rats. The effect might be one of the main ways to reduce urinary protein excretion.

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