Rutin mitigates hepatic fibrogenesis and inflammation through targeting TLR4 and P2X7 receptor signaling pathway in vitro and in vivo

Hou, Li‐Shuang; Cui, Zhenyu; Sun, Peng; Piao, Hu‐Ri; Han, Xin; Jiang, Song; Wang, Ge; Zheng, Shuang; Dong, Xiu-Xiu; Zhu, Yue; Lian, Li-Hua; Nan, Ji‐Xing; Wu, Yan-Ling

doi:10.1016/j.jff.2019.103700

Cited by 27 publications

(18 citation statements)

References 37 publications

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“…In contrast to gap junctions, which typically open under physiological conditions, undocked connexons, also termed hemichannels, have a low open probability and open in response to injury [ 10 ]. Altered hemichannel activity is associated with the pathophysiology of multiple disease states, with evidence linking altered cell-to-cell communication to increased senescence [ 54 ], inflammation [ 34 , 55 , 56 ] and fibrosis [ 18 , 19 , 20 , 21 ]. Data from our own lab demonstrate that the predominant connexin isoform in the proximal tubule (Cx43) is up-regulated in advanced CKD and correlates with elevated levels of TGFβ1 and severity of fibrosis and inflammation [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…When unbound, connexons form hemichannels through which molecules, e.g., adenosine triphosphate (ATP), can be released into the local extracellular space to influence neighbouring cells via activation of purinoreceptors [ 11 ]. Expression of the purinergic P2X7 receptor (P2X7R) is upregulated in the renal tubules of individuals with diabetic kidney disease [ 12 ] and has been heavily implicated in the progression of fibrosis both in the kidney [ 13 , 14 , 15 , 16 , 17 ] and in other tissue types [ 18 , 19 , 20 , 21 ]. Unsurprisingly, targeting purinergic signalling has received considerable attention.…”

Section: Introductionmentioning

confidence: 99%

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Danegaptide Prevents TGFβ1-Induced Damage in Human Proximal Tubule Epithelial Cells of the Kidney

Squires

Price

Mouritzen

et al. 2021

IJMS

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Chronic kidney disease (CKD) is a global health problem associated with a number of comorbidities. Recent evidence implicates increased hemichannel-mediated release of adenosine triphosphate (ATP) in the progression of tubulointerstitial fibrosis, the main underlying pathology of CKD. Here, we evaluate the effect of danegaptide on blocking hemichannel-mediated changes in the expression and function of proteins associated with disease progression in tubular epithelial kidney cells. Primary human proximal tubule epithelial cells (hPTECs) were treated with the beta1 isoform of the pro-fibrotic cytokine transforming growth factor (TGFβ1) ± danegaptide. qRT-PCR and immunoblotting confirmed mRNA and protein expression, whilst a cytokine antibody array assessed the expression/secretion of proinflammatory and profibrotic cytokines. Carboxyfluorescein dye uptake and ATP biosensing measured hemichannel activity and ATP release, whilst transepithelial electrical resistance was used to assess paracellular permeability. Danegaptide negated carboxyfluorescein dye uptake and ATP release and protected against protein changes associated with tubular injury. Blocking Cx43-mediated ATP release was paralleled by partial restoration of the expression of cell cycle inhibitors, adherens and tight junction proteins and decreased paracellular permeability. Furthermore, danegaptide inhibited TGFβ1-induced changes in the expression and secretion of key adipokines, cytokines, chemokines, growth factors and interleukins. The data suggest that as a gap junction modulator and hemichannel blocker, danegaptide has potential in the future treatment of CKD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Danegaptide Prevents TGFβ1-Induced Damage in Human Proximal Tubule Epithelial Cells of the Kidney

Squires

Price

Mouritzen

et al. 2021

IJMS

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“…Hemichannels permit the release of small molecules (<1 kDa), e.g., adenosine triphosphate (ATP), into the local extracellular environment, where it can influence neighbouring cells via activation of purinoreceptors [ 12 ]. Expression of the purinergic P2X7 receptor (P2X7R) is upregulated in renal tubules of individuals with diabetic kidney disease [ 13 ], and has been heavily implicated in both progression of fibrosis in the kidney [ 14 , 15 , 16 , 17 ] and in other tissue types [ 18 , 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Collagen I Modifies Connexin-43 Hemichannel Activity via Integrin α2β1 Binding in TGFβ1-Evoked Renal Tubular Epithelial Cells

Potter

Price

Cliff

et al. 2021

IJMS

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Chronic Kidney Disease (CKD) is associated with sustained inflammation and progressive fibrosis, changes that have been linked to altered connexin hemichannel-mediated release of adenosine triphosphate (ATP). Kidney fibrosis develops in response to increased deposition of extracellular matrix (ECM), and up-regulation of collagen I is an early marker of renal disease. With ECM remodeling known to promote a loss of epithelial stability, in the current study we used a clonal human kidney (HK2) model of proximal tubular epithelial cells to determine if collagen I modulates changes in cell function, via connexin-43 (Cx43) hemichannel ATP release. HK2 cells were cultured on collagen I and treated with the beta 1 isoform of the pro-fibrotic cytokine transforming growth factor (TGFβ1) ± the Cx43 mimetic Peptide 5 and/or an anti-integrin α2β1 neutralizing antibody. Phase microscopy and immunocytochemistry observed changes in cell morphology and cytoskeletal reorganization, whilst immunoblotting and ELISA identified changes in protein expression and secretion. Carboxyfluorescein dye uptake and biosensing measured hemichannel activity and ATP release. A Cytoselect extracellular matrix adhesion assay assessed changes in cell-substrate interactions. Collagen I and TGFβ1 synergistically evoked increased hemichannel activity and ATP release. This was paralleled by changes to markers of tubular injury, partly mediated by integrin α2β1/integrin-like kinase signaling. The co-incubation of the hemichannel blocker Peptide 5, reduced collagen I/TGFβ1 induced alterations and inhibited a positive feedforward loop between Cx43/ATP release/collagen I. This study highlights a role for collagen I in regulating connexin-mediated hemichannel activity through integrin α2β1 signaling, ahead of establishing Peptide 5 as a potential intervention.

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“…The extensive use of rutin in clinical treatments has received much attention [ 1 , 2 ]. Rutin has antibacterial [ 3 ], antiviral [ 4 ], anti-tumor [ 5 ], and anti-inflammatory [ 6 ] properties.…”

Section: Introductionmentioning

confidence: 99%

Electrochemical determination of rutin by using NiFe2O4 nanoparticles-loaded reduced graphene oxide

Askari

Salarizadeh

Askari

2021

J Mater Sci: Mater Electron

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A binary transition metal oxide containing nickel and iron (NiFe 2 O 4 ) and hybridization of this nanomaterial with reduced graphene oxide (rGO) are synthesized by the hydrothermal method. X-ray diffraction (XRD) and Raman spectroscopy confirm the successful synthesis of these materials. Also, scanning electron microscope (SEM) and transmission electron microscope (TEM) images illustrated the particle morphology with the particle size of 20 nm. The synthesized material is then examined as a sensor on the surface of the glassy carbon electrode to detect a very small amount of rutin. Some electrochemical tests such as cyclic voltammetry, differential pulse voltammetry (DPV), and impedance spectroscopy indicate the remarkable accuracy of this sensor and its operation in a relatively wide range of concentrations of rutin (100 nM-100 µM). The accuracy of the proposed electrochemical sensors is approximately 100 nM in 0.1 M PBS, (pH = 3) which is relatively impressive and can be reported. Also, the stability rate after 100 DPV was about 95 %, which is a considerable and relatively excellent value. Considering the very good results, it seems that the NiFe 2 O 4 -rGO can be considered as a new proposal in the development of accurate and inexpensive electrochemical sensors.

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Rutin mitigates hepatic fibrogenesis and inflammation through targeting TLR4 and P2X7 receptor signaling pathway in vitro and in vivo

Cited by 27 publications

References 37 publications

Danegaptide Prevents TGFβ1-Induced Damage in Human Proximal Tubule Epithelial Cells of the Kidney

Danegaptide Prevents TGFβ1-Induced Damage in Human Proximal Tubule Epithelial Cells of the Kidney

Collagen I Modifies Connexin-43 Hemichannel Activity via Integrin α2β1 Binding in TGFβ1-Evoked Renal Tubular Epithelial Cells

Electrochemical determination of rutin by using NiFe2O4 nanoparticles-loaded reduced graphene oxide

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