The Protective Effect of Beraprost Sodium on Diabetic Nephropathy by Inhibiting Inflammation and p38 MAPK Signaling Pathway in High-Fat Diet/Streptozotocin-Induced Diabetic Rats

Li, Peng; Li, Jie; Xu, Yixing; Wang, Yangtian; Du, Hong; Shao, Jianghua; Liu, Zhimin

doi:10.1155/2016/1690474

Cited by 31 publications

(31 citation statements)

References 49 publications

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“…Previous study reported that BPS ameliorated proteinuria and renal histologic lesions in diabetic rats. 24 Experimental study documented that BPS had a beneficial effect on DN. 25 Recent study demonstrated that BPS attenuated characteristics of metabolic syndrome in obese rats.…”

Section: Discussionmentioning

confidence: 99%

<p>Panax Notoginseng Ameliorates Podocyte EMT by Targeting the Wnt/β-Catenin Signaling Pathway in STZ-Induced Diabetic Rats</p>

Xie¹,

Zhai²,

Chen³

et al. 2020

DDDT

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Introduction: Epithelial-mesenchymal transition (EMT) may contribute to podocyte dysfunction in diabetic nephropathy (DN). Aiming to identify novel therapeutic options, we investigated the protective effects of Panax notoginseng (PN) on podocyte EMT in diabetic rats and explored its mechanisms. Methods: Diabetes was induced in rats with streptozotocin (STZ) by intraperitoneal injection at 55 mg/kg. Diabetic rats were randomly divided into three groups, namely, diabetic rats, diabetic rats treated with beraprost sodium (BPS) at 0.6 mg/kg/d or PN at 0.4 g/kg/d p. o., for 12 weeks. Urinary albumin/creatinine ratio (ACR), biochemical parameters, renal histopathology, and podocyte morphological changes were evaluated. Protein expression of EMT markers (desmin, α-SMA, and nephrin) as well as components of the Wnt/β-catenin pathway (wnt1, β-catenin, and snail) was detected by immunohistochemistry and Western blot, respectively. Results: In diabetic rats, severe hyperglycemia and albuminuria were detected. Moreover, mesangial expansion and podocyte foot process effacement were found markedly increased in diabetic kidneys. Increased protein expression of wnt1, β-catenin, snail, desmin, and α-SMA, as well as decreased protein expression of nephrin was detected in diabetic kidneys. All these abnormalities found in DN rats were partially restored by PN treatment. Conclusion: PN ameliorated albuminuria and podocyte EMT in diabetic rats partly through inhibiting Wnt/β-catenin signaling pathway. These findings provide experimental arguments for a novel therapeutic option in DN.

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Section: Discussionmentioning

confidence: 99%

<p>Panax Notoginseng Ameliorates Podocyte EMT by Targeting the Wnt/β-Catenin Signaling Pathway in STZ-Induced Diabetic Rats</p>

Xie¹,

Zhai²,

Chen³

et al. 2020

DDDT

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“…Furthermore, Peng et al. reported that intraperitoneal administration of PGI 2 in type 2 diabetes rats inhibited the p38 mitogen‐activated protein kinases signaling pathway in kidney tissue, reduced inflammatory cytokines and suppressed excretion of albumin. Thus, numerous studies reported on various cytokines that show renoprotective action.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of adipose‐derived mesenchymal stem cell sheets directly into the kidney suppresses the progression of renal injury in a diabetic nephropathy rat model

Takemura

Shimizu

Oka

et al. 2019

J of Diabetes Invest

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Aims/Introduction: Adipose-derived mesenchymal stem cell (ASC) transplantation is a promising therapy for diabetic nephropathy (DN). However, intravascular administration of ASCs is associated with low engraftment in target organs. Therefore, we considered applying the cell sheet technology to ASCs. In this study, ASC sheets were directly transplanted into the kidneys of a DN rat model, and therapeutic consequences were analyzed. Materials and Methods: Adipose-derived mesenchymal stem cells were isolated from adipose tissues of 7-week-old enhanced green fluorescent protein rats, and ASC sheets were prepared using a temperature-responsive culture dish. A DN rat model was established from 5-week-old Spontaneously Diabetic Torii fatty rats. Seven-week-old DN rats (n = 21) were assigned to one of the following groups: sham-operated (n = 6); ASC suspension (6.0 9 10 6 cells/mL) administered intravenously (n = 7); six ASC sheets transplanted directly into the kidney (n = 8). The therapeutic effect of the cell sheets was determined based on urinary biomarker expression and histological analyses. Results: The ASC sheets survived under the kidney capsule of the DN rat model for 14 days after transplantation. Furthermore, albuminuria and urinary tumor necrosis factor-a levels were significantly lower in the ASC sheets transplanted directly into the kidney group than in the sham-operated and ASC suspension administered intravenously groups (P < 0.05). Histologically, the ASC sheets transplanted directly into the kidney group presented mild atrophy of the proximal tubule and maintained the renal tubular structure. Conclusions: Transplantation of ASC sheets directly into the kidney improved transplantation efficiency and suppressed renal injury progression. Therefore, the ASC sheet technology might be a promising novel treatment for DN.Although strict glycemic control is reported to suppress the progression of DN 6,7 , there is no treatment to stop DN progression. Recently, mesenchymal stem cell (MSC) transplantation has received substantial attention as a therapy for DN. MSCs can differentiate into adipogenic and osteogenic cells 8 , and possess clinically useful properties, such as low antigenicity 9,10 and paracrine effects through cytokines 11,12 . In particular, adipose-derived mesenchymal stem cells (ASCs) represent an attractive cell source owing to their abundance in the body 13,14 .In animal experiments on DN, intravascular administration of ASC suspensions was shown to suppress the progression of

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“…SAA inhibits activation of the NF-κB and p38 MAPK signaling pathways in 5/6Nx rats Several studies have suggested that the NF-κB and p38 MAPK signaling pathways are closely associated with kidney inflammation [13,[20][21][22][23]. Thus, levels of major proteins of the NF-κB and p38 MAPK signaling pathways were measured during CKD.…”

Section: Biochemical Parameters In Experimental Animalsmentioning

confidence: 99%

“…It has been reported that the activation of p38 mitogenactivated protein kinase (MAPK), a member of the family of MAPKs, plays a key role in kidney inflammation [22,23]. The activation of p38 MAPK can promote the production of proinflammatory cytokines and regulate cellular apoptosis during renal injury.…”

Section: Introductionmentioning

confidence: 99%

Salvianolic acid A attenuates kidney injury and inflammation by inhibiting NF-κB and p38 MAPK signaling pathways in 5/6 nephrectomized rats

et al. 2018

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Salvianolic acid A (SAA) is a minor phenolic carboxylic acid extracted from Salviae miltiorrhizae Bunge (Danshen). SAA exhibits a variety of pharmacological activities, such as antioxidative, anti-thrombotic, neuroprotective, and anti-fibrotic effects, as well as protection from myocardial ischemia and prevention of diabetes and other diseases. Furthermore, SAA has shown renal-protective effects in doxorubicin-induced nephropathy. However, there has been limited research regarding the effects of SAA and underlying mechanisms in chronic kidney disease (CKD). Here, we examined the effects and molecular mechanisms of SAA in an established animal model of 5/6 nephrectomized (5/6Nx) rats. The rats were injected with SAA (2.5, 5, and 10 mg/kg per day, intraperitoneally (ip)) for 28 days. SAA dose-dependently lowered the levels of urine protein, blood urea nitrogen, serum creatinine, plasma total cholesterol, and plasma triglycerides in 5/6Nx rats. Histological examination revealed that SAA dose-dependently attenuated renal pathological lesions, evidenced by reduced renal tubulointerstitial fibrosis by decreasing the expression levels of tumor growth factor-β1 and α-smooth muscle actin in 5/6Nx rats. Moreover, SAA dose-dependently inhibited the activation of nuclear factor-κB (NF-κB) and p38 mitogen-activated protein kinase (MAPK) signaling pathways, subsequently attenuating the secretion of tumor necrosis factor-α and interleukin-1β and inhibiting the expression of monocyte chemotactic protein-1, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in kidneys of 5/6Nx rats. The above results were consistent with those obtained in lipopolysaccharide-induced HK-2 cells in vitro (a recognized in vitro inflammatory model). In conclusion, our results demonstrated that SAA effectively attenuates kidney injury in 5/6Nx rats. The therapeutic effects of SAA on kidney injury can be attributed to its anti-inflammatory activities through inhibition of the activation of the NF-κB and p38 MAPK signaling pathways.

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The Protective Effect of Beraprost Sodium on Diabetic Nephropathy by Inhibiting Inflammation and p38 MAPK Signaling Pathway in High-Fat Diet/Streptozotocin-Induced Diabetic Rats

Cited by 31 publications

References 49 publications

<p>Panax Notoginseng Ameliorates Podocyte EMT by Targeting the Wnt/β-Catenin Signaling Pathway in STZ-Induced Diabetic Rats</p>

<p>Panax Notoginseng Ameliorates Podocyte EMT by Targeting the Wnt/β-Catenin Signaling Pathway in STZ-Induced Diabetic Rats</p>

Transplantation of adipose‐derived mesenchymal stem cell sheets directly into the kidney suppresses the progression of renal injury in a diabetic nephropathy rat model

Salvianolic acid A attenuates kidney injury and inflammation by inhibiting NF-κB and p38 MAPK signaling pathways in 5/6 nephrectomized rats

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