Inflammation in Diabetic Nephropathy

Lim, Andy; Tesch, Gregory H

doi:10.1155/2012/146154

Cited by 363 publications

(327 citation statements)

References 144 publications

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“…These events facilitate the kidney infiltration of monocytes and lymphocytes, which become activated in diabetic kidney and secrete proinflammatory cytokines. This leukocyte activity amplifies the inflammatory response and promotes cellular injury and the development of fibrosis (11). Our findings in this study suggest that in diabetic rat kidney, H 2 S attenuates oxidative stress and inflammation, which might be two important protective mechanisms against diabetic nephropathy.…”

Section: Discussionmentioning

confidence: 55%

Hydrogen Sulfide Alleviates Diabetic Nephropathy in a Streptozotocin-induced Diabetic Rat Model

Zhou¹,

Yu²,

Zhan

et al. 2014

Journal of Biological Chemistry

134

109

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Background: H 2 S plays critical roles in the pathogenesis of chronic kidney diseases. Results: H 2 S improved renal function and attenuated glomerular basement membrane thickening, mesangial matrix deposition, and renal interstitial fibrosis in diabetic rats. Conclusion: H 2 S attenuates oxidative stress and inflammation, reduces mesangial cell proliferation, and inhibits the reninangiotensin system in diabetic kidney. Significance: H 2 S alleviates the development of diabetic nephropathy.

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Section: Discussionmentioning

confidence: 55%

Hydrogen Sulfide Alleviates Diabetic Nephropathy in a Streptozotocin-induced Diabetic Rat Model

Zhou¹,

Yu²,

Zhan

et al. 2014

Journal of Biological Chemistry

134

109

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“…10,46,47 Macrophages are among the major inflammatory/ immune cells that infiltrate into the kidneys under diabetic conditions and create a proinflammatory environment. 21 This in turn affects almost all renal cells, contributing to ECM accumulation, fibrosis, cellular dysfunction, and eventually proteinuria.…”

Section: Discussionmentioning

confidence: 99%

“…The development and progression of DN are highly complex, with diverse renal cells, including podocytes and endothelial, mesangial, and tubular cells, affected. 3 Additionally, immune cells, 47 especially macrophages, 21 infiltrate the kidneys during DN. Interestingly, miR-146a is highly expressed in macrophages and can negatively regulate macrophage inflammation, 34 which prompted us to determine its expression and function in diabetic macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…21,57 The low but significantly elevated levels of circulating inflammatory mediators are thought to contribute to monocyte/macrophage activation. 47 At the same time, macrophage polarization is also altered. To study the role of miR-146a in these early events, we isolated murine peritoneal macrophages after 4 weeks of diabetes induction from both WT and miR-146a 2/2 mice in order to examine the phenotype of macrophages using gene expression analysis.…”

Section: Discussionmentioning

confidence: 99%

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Anti-Inflammatory Role of MicroRNA-146a in the Pathogenesis of Diabetic Nephropathy

Bhatt

Lanting

Jia

et al. 2015

JASN

159

130

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Inflammation has a critical role in the pathogenesis of diabetic complications, including diabetic nephropathy (DN). MicroRNAs have recently emerged as important regulators of DN. However, the role of microRNAs in the regulation of inflammation during DN is poorly understood. Here, we examined the in vivo role of microRNA-146a (miR-146a), a known anti-inflammatory microRNA, in the pathogenesis of DN. In a model of streptozotocin-induced diabetes, miR-146a 2/2 mice showed significantly exacerbated proteinuria, renal macrophage infiltration, glomerular hypertrophy, and fibrosis relative to the respective levels in control wild-type mice. Diabetes-induced upregulation of proinflammatory and profibrotic genes was significantly greater in the kidneys of miR-146a 2/2 than in the kidneys of wild-type mice. Notably, miR146a expression increased in both peritoneal and intrarenal macrophages in diabetic wild-type mice. Mechanistically, miR-146a deficiency during diabetes led to increased expression of M1 activation markers and suppression of M2 markers in macrophages. Concomitant with increased expression of proinflammatory cytokines, such as IL-1b and IL-18, markers of inflammasome activation also increased in the macrophages of diabetic miR-146a 2/2 mice. These studies suggest that in early DN, miR-146a upregulation exerts a protective effect by downregulating target inflammation-related genes, resulting in suppression of proinflammatory and inflammasome gene activation. Loss of this protective mechanism in miR-146a 2/2 mice leads to accelerated DN. Taken together, these results identify miR-146a as a novel anti-inflammatory noncoding RNA modulator of DN. 27: 227727: -228827: , 201627: . doi: 10.1681 Diabetic nephropathy (DN) is the leading cause of CKD and ESRD. 1-6 Development and progression of DN involve a complex interplay among metabolic, hemodynamic, growth, and inflammatory factors. 1,3,[7][8][9][10][11][12][13] The progressive decline in renal function during DN is a result of a multitude of pathologic changes in the kidneys, including glomerular and tubular hypertrophy, macrophage infiltration, extracellular matrix (ECM) accumulation in multiple renal cells, mesangial expansion, endothelial dysfunction, and podocyte injury. 1,3,[7][8][9][10][11][12][14][15][16] These pathologic changes clinically manifest as proteinuria and a steady deterioration in GFR. 3,4,16 Identification of molecular pathways that contribute to the pathophysiology of DN is imperative for the development of new therapeutic strategies. J Am Soc NephrolConversely, identification of factors that exert adaptive and protective roles in the early stages of DN can be exploited to prevent progression to ESRD.

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“…Once macrophages have activated, they can release nitric oxide, ROS, IL-1, TNF-α, complement factors, and Metalloproteinases (MMPs), all of which promote renal injury [47]. Besides, T-cells express the receptor for AGEs and the activation of CD4+ and CD8+ T-cells by AGE can initiate Interferon (IFN)-γ secretion by T-cells, which could induce further inflammation and oxidative stress within the diabetic kidney [48]. Although, CD8+ cells may perform a cytolytic function in the diabetic kidney [49], the function of CD8+ T-cells, however, becomes more significant at later stages of the disease when tissue loss is evident [50].…”

Section: Macrophage/lymphocyte Sharing and Interactionmentioning

confidence: 99%

Microinflammation as a Candidate for Diabetic Nephropathy

hafez

2014

Interdiscip J Microinflammation

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Diabetic Nephropathy (DN) is a major cause of mortality in patients with Type 1 and 2 diabetes throughout the world. This review draws attention to the important role of microinflammation and the complex pathways implicated in the development and progression of DN. These pathways include the collaboration of metabolic, hemodynamic and hormonal factors with oxidative stress in patients with genetic susceptibility to create an inflammatory milieu. The key role of inflammatory cells in the kidney, particularly infiltrating macrophages and T-lymphocytes is highlighted. The major inflammatory cytokines and chemokines, receptors, adhesion molecules as well as transcription factors and transduction pathways involved in the pathogenesis of DN are also discussed. Understanding of these inflammatory pathways guides important therapeutic appliances and improves the discovery of new therapeutic targets that can be translated into clinical treatments for DN.

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Inflammation in Diabetic Nephropathy

Cited by 363 publications

References 144 publications

Hydrogen Sulfide Alleviates Diabetic Nephropathy in a Streptozotocin-induced Diabetic Rat Model

Hydrogen Sulfide Alleviates Diabetic Nephropathy in a Streptozotocin-induced Diabetic Rat Model

Anti-Inflammatory Role of MicroRNA-146a in the Pathogenesis of Diabetic Nephropathy

Microinflammation as a Candidate for Diabetic Nephropathy

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