Connections in chronic kidney disease: connexin 43 and connexin 37 interaction

José, Pedro A.; Chen, Shiyou; Armando, Inés

doi:10.1152/ajprenal.00204.2011

Cited by 5 publications

(3 citation statements)

References 36 publications

(33 reference statements)

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“…The downregulation of KLF7 was likewise negatively associated with DNA hypermethylation, suggesting that DNA methylation plays an important role in KLF7 expression. The results also indicated that the expression of Gja4, or connexin-37, was upregulated by TGF-β, which is consistent with other prior reports (Ota et al, 2002; Jose et al, 2011). Further, the DNA hypomethylation in Gja4 suggested that methylation plays a critical role in the negative regulation of Gja4 expression.…”

Section: Resultssupporting

confidence: 92%

The Use of Targeted Next Generation Sequencing to Explore Candidate Regulators of TGF-β1’s Impact on Kidney Cells

Wang

Ji²,

Naeem

et al. 2018

Front. Physiol.

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Aims/Hypothesis: Transforming growth factor-beta (TGF-β1) plays an important regulatory role in the progression of chronic kidney failure. Further, damage to kidney glomerular mesangial cells is central to the progression of diabetic nephropathy. The aim of this study was to explore the genetic associations between mRNA, microRNA, and epigenetics in mesangial cells in response to TGF-β1.Methods: The regulatory effects of TGF-β1 on mesangial cells were investigated at different molecular levels by treating mesangial cells with TGF-β1 for 3 days followed by genome-wide miRNA, RNA, DNA methylation, and H3K27me3 expression profiling using next generation sequencing (NGS).Results: Our results provide the first comprehensive, computationally integrated report of RNA-Seq, miRNA-Seq, and epigenomic analyses across all genetic variations, confirming the occurrence of DNA methylation and H3K27me3 in response to TGF-β1. Our findings show that the expression of KLF7 and Gja4 are involved in TGF-β1 regulated DNA methylation. Our data also provide evidence of the association between epigenetic changes and the expression of genes closely related to TGF-β1 regulation.Conclusion: This study has advanced our current knowledge of mechanisms that contribute to the expression of TGF-β1-regulated genes involved in the pathogenesis of kidney disease. The molecular underpinnings of TGF-β1 stimulation of kidney cells was determined, thereby providing a robust platform for further target exploration.

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Section: Resultssupporting

confidence: 92%

The Use of Targeted Next Generation Sequencing to Explore Candidate Regulators of TGF-β1’s Impact on Kidney Cells

Wang

Ji²,

Naeem

et al. 2018

Front. Physiol.

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“…Considering the presence of connexins within the kidney and their functional role in growth regulation [8,[11][12][13], analysis of connexins provides a new viewpoint for investigating CKD. Connexins are a multi-gene family of transmembrane proteins with ~20 isoforms.…”

Section: Introductionmentioning

confidence: 99%

Beyond Gap Junction Channel Function: the Expression of Cx43 Contributes to Aldosterone-Induced Mesangial Cell Proliferation via the ERK1/2 and PKC Pathways

Zhang

Han

Wang³

et al. 2015

Cell Physiol Biochem

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Aims: This study aimed to explore the precise mechanism and signaling pathways of mesangial cell (MC) proliferation from a new point of view considering Connexin 43 (Cx43). Methods: MC proliferation was measured by the incorporation of 3H-thymidine (3H-TdR). Cx43 was over-expressed in MC cells using lipofectamine 2000, and the expression level was tested with reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses. The gap junction channel function was explored by Lucifer Yellow scrape loading and dye transfer (SLDT), and the intracellular calcium concentrations ([Ca²⁺]_i) were characterized by confocal microscopy on cells loaded with Fura-3/AM. Results: There was an inverse correlation between Cx43 expression and MC proliferation (P<0.05). SLDT studies revealed that there was no difference in the gap junction channel function between the normal and Aldosterone (Aldo)-stimulated groups (P>0.05). Our data also showed that the mineralcorticoid receptor (MR) antagonist spironolactone, ERK1/2 inhibitor PD98059 and PKC inhibitor GF109203X could attenuate the down-regulation of Cx43 expression in Aldo-induced MC proliferation; however, the PI3K inhibitor LY294002 could block MC proliferation without affecting Cx43 expression at either the mRNA or protein level. In addition, Aldo promoted MC proliferation in parallel with increasing [Ca²⁺]_i (P<0.05), suggesting that the classical PKC pathway might be activated. Conclusions: Our study provides preliminary evidence that Cx43 is an important regulator of Aldo-promoted MC proliferation. Furthermore, reduced Cx43 expression promoted MC proliferation independent of the gap junction channel function, and this process might be mediated through the ERK1/2- and PKC-dependent pathways.

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“…In our study, in the yotari cortex at P14, Cx37 expression was lower in regard to Cx43. In a study by Jose et al, an increase in the Cx43/Cx37 ratio was shown to be a regulator of renal fibrosis [ 33 ]. Additionally, propagation of vasodilatation was decreased in Cx40 knockout mice, while in Cx37 knockout mice propagation of vasoconstriction was observed [ 1 ].…”

Section: Discussionmentioning

confidence: 99%

Alteration of Cx37, Cx40, Cx43, Cx45, Panx1, and Renin Expression Patterns in Postnatal Kidneys of Dab1-/- (yotari) Mice

Lozić

Filipović

Jurić

et al. 2021

IJMS

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Numerous evidence corroborates roles of gap junctions/hemichannels in proper kidney development. We analyzed how Dab1 gene functional silencing influences expression and localization of Cx37, Cx40, Cx43, Cx45, Panx1 and renin in postnatal kidneys of yotari mice, by using immunohistochemistry and electron microscopy. Dab1 Δ102/221 might lead to the activation of c-Src tyrosine kinase, causing the upregulation of Cx43 in the medulla of yotari mice. The expression of renin was more prominent in yotari mice (p < 0.001). Renin granules were unusually present inside the vascular walls of glomeruli capillaries, in proximal and distal convoluted tubules and in the medulla. Disfunction of Cx40 is likely responsible for increased atypically positioned renin cells which release renin in an uncontrolled fashion, but this doesn’t rule out simultaneous involvement of other Cxs, such as Cx45 which was significantly increased in the yotari cortex. The decreased Cx37 expression in yotari medulla might contribute to hypertension reduction provoked by high renin expression. These findings imply the relevance of Cxs/Panx1 as markers of impaired kidney function (high renin) in yotari mice and that they have a role in the preservation of intercellular signaling and implicate connexopathies as the cause of premature death of yotari mice.

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Connections in chronic kidney disease: connexin 43 and connexin 37 interaction

Cited by 5 publications

References 36 publications

The Use of Targeted Next Generation Sequencing to Explore Candidate Regulators of TGF-β1’s Impact on Kidney Cells

The Use of Targeted Next Generation Sequencing to Explore Candidate Regulators of TGF-β1’s Impact on Kidney Cells

Beyond Gap Junction Channel Function: the Expression of Cx43 Contributes to Aldosterone-Induced Mesangial Cell Proliferation via the ERK1/2 and PKC Pathways

Alteration of Cx37, Cx40, Cx43, Cx45, Panx1, and Renin Expression Patterns in Postnatal Kidneys of Dab1-/- (yotari) Mice

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