Notch Signaling Molecules Activate TGF-<i>β</i>in Rat Mesangial Cells under High Glucose Conditions

Liu, Li; Gao, Chenlin; Guo, Chenchen; Li, Xia; Li, Jia; Wan, Qin; Xu, Yong

doi:10.1155/2013/979702

Cited by 18 publications

(17 citation statements)

References 29 publications

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Section: Notch and Epithelial-mesenchymal Transitionmentioning

confidence: 99%

“…Thus Notch signaling molecules are reported to activate TGFβ in rat mesangial cells under hyperglycemic conditions [55]. Given the role of TGFβ in promotion of EMT, the potential significance of Notch signaling in this process is suggested [53, 55]. Since EMT is associated with chronic fibrosis in the kidney [54], lung [56-59], liver [49, 60] and heart[61-63] evidence for Notch signaling in EMT focused on epithelial cells derived these tissues.…”

Section: Notch and Epithelial-mesenchymal Transitionmentioning

confidence: 99%

See 1 more Smart Citation

Notch in fibrosis and as a target of anti-fibrotic therapy

Phan

2016

Pharmacological Research

102

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The Notch pathway represents a highly conserved signaling network with essential roles in regulation of key cellular processes and functions, many of which are critical for development. Accumulating evidence indicates that it is also essential for fibrosis and thus the pathogenesis of chronic fibroproliferative diseases in diverse organs and tissues. Different effects of Notch activation are observed depending on cellular and tissue context as well as in both physiologic and pathologic states. Close interactions of Notch signaling pathway with other signaling pathways have been identified. In this review, current knowledge on the role of the Notch signaling with special focus on fibrosis and its potential as a therapeutic target is summarized.

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Section: Notch and Epithelial-mesenchymal Transitionmentioning

confidence: 99%

Section: Notch and Epithelial-mesenchymal Transitionmentioning

confidence: 99%

Notch in fibrosis and as a target of anti-fibrotic therapy

Phan

2016

Pharmacological Research

102

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“…Further support for this notion was derived from the fact that treatment with Notch signaling inhibitors leads to amelioration of tubulo-interstitial fibrosis and dampened the progression of diabetic nephropathy [34]. Besides the tubulo-interstitium, Liu et al discovered that high glucose (HG) also increases the expression of Notch1, Jagged1 and Hes1 along with the profibrogenic cytokine, TGF-β, and ECM protein fibronectin in rat glomerular mesangial cells [35]. The Notch signaling pathway also exerts its effects on podocytes and thus plays an important role in DN development [36].…”

Section: Notch and Ecmmentioning

confidence: 99%

Insights into the Mechanisms Involved in the Expression and Regulation of Extracellular Matrix Proteins in Diabetic Nephropathy

Hu¹,

Sun²,

Xiao³

et al. 2015

CMC

166

113

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Diabetic Nephropathy (DN) is believed to be a major microvascular complication of diabetes. The hallmark of DN includes deposition of Extracellular Matrix (ECM) proteins, such as, collagen, laminin and fibronectin in the mesangium and renal tubulo-interstitium of the glomerulus and basement membranes. Such an increased expression of ECM leads to glomerular and tubular basement membranes thickening and increase of mesangial matrix, ultimately resulting in glomerulosclerosis and tubulointerstitial fibrosis. The characteristic morphologic glomerular mesangial lesion has been described as Kimmelstiel–Wilson nodule, and the process at times is referred to as diabetic nodular glomerulosclerosis. Thus, the accumulation of ECM proteins plays a critical role in the development of DN. The relevant mechanism(s) involved in the increased ECM expression and their regulation in the kidney in diabetic state has been extensively investigated and documented in the literature. Nevertheless, there are certain other mechanisms that may yet be conclusively defined. Recent studies demonstrated that some of the new signaling pathways or molecules including, Notch, Wnt, mTOR, TLRs and small GTPase may play a pivotal role in the modulation of ECM regulation and expression in DN. Such modulation could be operational for instance Notch though Notch1/Jagged1 signaling, Wnt by Wnt/β-catenin pathway and mTOR via PI3-K/Akt/mTOR signaling pathways. All these pathways may be critical in the modulation of ECM expression and tubulo-interstitial fibrosis. In addition, TLRs, mainly the TLR2 and TLR4, by TLR2-dependent and TGF-β-dependent conduits, may modulate ECM expression and generate a fibrogenic response. Small GTPase like Rho, Ras and Rab family by targeting relevant genes may also influence the accumulation of ECM proteins and renal fibrosis in hyperglycemic states. This review summarizes the recent information about the role and mechanisms by which these molecules and signaling pathways regulate ECM synthesis and its expression in high glucose ambience in vitro and in vivo states. The understanding of such signaling pathways and the molecules that influence expression, secretion and amassing of ECM may aid in developing strategies for the amelioration of diabetic nephropathy.

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“…In addition, high ambient glucose increases TGF-b 1 mRNA and protein levels in cultured proximal tubular cells, glomerular epithelial and mesangial cells [19]. Neutralizing anti-TGF-b 1 antibodies or antisense TGF-b 1 oligodeoxynucleotides prevent the hypertrophic effects of high glucose and inhibit matrix synthesis in renal cells.…”

Section: Introductionmentioning

confidence: 99%