Hyperglycemia activates the renin-angiotensin system and induces epithelial-mesenchymal transition in streptozotocin-induced diabetic kidneys

Chen, Chung-Ming; Juan, Shu Hui; Chou, Hsiu Chu

doi:10.1177/1470320318803009

Cited by 24 publications

(18 citation statements)

References 46 publications

(48 reference statements)

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“…In this study, we extensively investigated the mechanisms responsible for the therapeutic effects of JSD on DN, particularly focusing on liver and kidney dysfunction. Hyperglycemia induces renal injury through multiple pathways, including insulin resistance, glucose metabolism, hemodynamic disorders, inflammation, and fibrosis [29]. After long-term and chronic kidney damage in DN, incomplete tubular recovery leads to renal fibrosis and destroyed renal function.…”

Section: Discussionmentioning

confidence: 99%

Jowiseungki decoction affects diabetic nephropathy in mice through renal injury inhibition as evidenced by network pharmacology and gut microbiota analyses

Meng

Kang

et al. 2020

Chin Med

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Background: Jowiseungki decoction (JSD) is a prescription commonly used for the treatment of diabetic complications or diabetic nephropathy (DN) in traditional medicine clinics. However, the underlying therapeutic mechanisms of JSD are still unclear. Methods: Streptozotocin (STZ)-induced DN mice were administered 100 and 500 mg/kg JSD for 4 weeks, and the therapeutic mechanisms and targets of JSD were analyzed by network pharmacology and gut microbiota analyses. Results: JSD significantly decreased the increase in food and water intake, urine volume, fasting blood glucose, serum glucose and triglyceride levels, and urinary albumin excretion. JSD administration significantly increased the decrease in insulin secretion and creatinine clearance and reduced the structural damage to the kidney tissues. Moreover, JSD administration significantly inhibited the expression of protein kinase C-alpha (PKC-α), transforming growth factor beta-1 (TGF-β1), α-smooth muscle actin (α-SMA), nuclear factor-κB (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in the kidney tissues of DN mice, while it significantly increased the phosphorylation of insulin receptor substrate 1 (IRS-1), phosphatidylinositol-3-kinase (PI3K), and protein kinase B (Akt). In the network pharmacological analysis, JSD obviously influenced phosphatase binding, protein serine/threonine kinase, and mitogen-activated protein kinase (MAPK)-related signaling pathways. Our data suggest that JSD can improve symptoms in STZ-induced DN mice through the inhibition of kidney dysfunction, in particular, by regulating the PKCα/PI3K/Akt and NF-κB/α-SMA signaling pathways. Gut microbiota analysis can help to discover the pharmacomechanisms of the influence of JSD on bacterial diversity and flora structures in DN. Conclusion: JSD can improve the symptoms of DN, and the underlying mechanism of this effect is renal protection through the inhibition of fibrosis and inflammation. JSD can also change bacterial diversity and community structures in DN.

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Section: Discussionmentioning

confidence: 99%

Jowiseungki decoction affects diabetic nephropathy in mice through renal injury inhibition as evidenced by network pharmacology and gut microbiota analyses

Meng

Kang

et al. 2020

Chin Med

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“…Activation of ATR1 plays an important role in the pathogenesis of renal tissue injury. In an earlier study, it has been observed that hyperglycemia activates RAAS and contributes to renal fibrosis [15]. Ang II, the major mediator of kidney injury, displays majority of its deteriorating effects like generation of ROS, tissue inflammation, and fibrosis via activation of ATR1 [16].…”

mentioning

confidence: 99%

Normoalbuminuric diabetic kidney disease: a distinct entity?

Madhu

2019

Int J Diabetes Dev Ctries

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“…It is well-known that inhibitors of the reninangiotensin system delay the progression of diabetic kidney disease 32,33 . Furthermore, numerous studies have observed activation of the RAS in subjects with type 2 diabetes [34][35][36][37] . RAS and type 2 diabetes are closely related.…”

Section: Discussionmentioning

confidence: 99%

An association study of C9orf3, a novel component of the renin-angiotensin system, and hypertension in diabetes

Ichikawa

Konoshita

Makino

et al. 2020

Sci Rep

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The renin-angiotensin system (RAS) is important in the onset and course of cardiovascular, kidney, and metabolic disorders. Previous reports showed that the RAS blockade protects organs and suppress the development of type 2 diabetes mellitus. A novel component of the RAS, namely, chromosome 9 open reading frame 3 (C9orf3), was recently identified, however, its effects are unclear. We evaluated whether the genetic variant of C9orf3 is associated with morbidity of hypertension among subjects with type 2 diabetes. We enrolled 382 subjects with type 2 diabetes, 222 of whom were diagnosed with hypertension. Human leukocyte genomic DNA was isolated and a genetic variant was analyzed for a C/T variant of C9orf3 (rs4385527) via PCR analysis. The relationship between the genotype and hypertension morbidity among subjects with diabetes was examined. The proportion of the respective C9orf3 genetic variants were as follows 247 CC, 119 CT, and 16 TT. The risk of hypertension was determined to be 1.58, with a 95% confidence interval of 1.11–2.27. Moreover, the p value was 0.012 for allelic comparison and for Armitage’s trend test, with the C allele identified as the risk factor. Consequently, hypertension was markedly associated with type 2 diabetes in subjects with the C9orf3 variant, exhibiting a nearly 1.6-fold increased risk. The C variant of a new component of the RAS, C9orf3 (rs4385527) might have a considerable impact on the pathogenesis of hypertension in diabetes.

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Hyperglycemia activates the renin-angiotensin system and induces epithelial-mesenchymal transition in streptozotocin-induced diabetic kidneys

Cited by 24 publications

References 46 publications

Jowiseungki decoction affects diabetic nephropathy in mice through renal injury inhibition as evidenced by network pharmacology and gut microbiota analyses

Jowiseungki decoction affects diabetic nephropathy in mice through renal injury inhibition as evidenced by network pharmacology and gut microbiota analyses

Normoalbuminuric diabetic kidney disease: a distinct entity?

An association study of C9orf3, a novel component of the renin-angiotensin system, and hypertension in diabetes

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