Endothelial-specific deletion of connexin 43 improves renal function and structure after acute kidney injury
Abstract Background We have previously reported that the gap junction protein connexin 43 (Cx43) was upregulated in chronic renal disease in humans and rodents and plays a crucial role in the progression of experimental nephropathy. In this study, we investigated its role after renal ischemia/reperf...
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2024-12-01
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| Online Access: | https://doi.org/10.1186/s10020-024-01011-6 |
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| author | Magali Genest Satoshi Kinugasa Elena Roger Louis Boutin Sandrine Placier Stefanny Figueroa Aude Dorison Safia Hadjadj Ines Baba Emmanuel L. Gautier Panagiotis Kavvadas Christos Chatziantoniou Christos E. Chadjichristos |
| author_facet | Magali Genest Satoshi Kinugasa Elena Roger Louis Boutin Sandrine Placier Stefanny Figueroa Aude Dorison Safia Hadjadj Ines Baba Emmanuel L. Gautier Panagiotis Kavvadas Christos Chatziantoniou Christos E. Chadjichristos |
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| description | Abstract Background We have previously reported that the gap junction protein connexin 43 (Cx43) was upregulated in chronic renal disease in humans and rodents and plays a crucial role in the progression of experimental nephropathy. In this study, we investigated its role after renal ischemia/reperfusion (rIR), which is a major mechanism of injury in acute renal injury (AKI) and renal transplant graft dysfunction. Methods Wild-type mice (WT) and mice in which Cx43 expression was genetically reduced by half (Cx43 ±) were unilaterally nephrectomized. The left renal artery was subsequently clamped, with reperfusion of varying duration. Mice with tubular- or endothelial-specific deletion of Cx43 were also used to assess the effect of this connexin in each cell type after rIR. Kidneys were assessed for histological evaluation, immunohistochemistry, and RT-PCR. Results Blood urea nitrogen and creatininemia were progressively elevated in WT mice and picked up 48 h after rIR. At the same time point, severe tubular necrosis and dilation occurred in the cortico-medullary junction of the injured kidneys with accompanying massive neutrophil infiltration. Interestingly, Cx43 expression was progressively increased within the tubulointerstitial compartment during kidney damage progression and was paralleled closely by that of markers of renal dysfunction. Cx43 ± mice showed fewer tubular lesions, less inflammation, and further improved renal function. Similar results were observed in mice where Cx43 was specifically deleted within the vascular endothelium. In contrast, Cx43 deletion in renal tubules did not significantly improve renal structure and function after rIR. Conclusion Our findings suggest that endothelial Cx43 plays a crucial role in AKI. |
| format | Article |
| id | doaj-art-83836f98d35c4a929e8c9c96697b0c4c |
| institution | Kabale University |
| issn | 1528-3658 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
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| series | Molecular Medicine |
| spelling | doaj-art-83836f98d35c4a929e8c9c96697b0c4c2024-12-22T12:32:15ZengBMCMolecular Medicine1528-36582024-12-0130111410.1186/s10020-024-01011-6Endothelial-specific deletion of connexin 43 improves renal function and structure after acute kidney injuryMagali Genest0Satoshi Kinugasa1Elena Roger2Louis Boutin3Sandrine Placier4Stefanny Figueroa5Aude Dorison6Safia Hadjadj7Ines Baba8Emmanuel L. Gautier9Panagiotis Kavvadas10Christos Chatziantoniou11Christos E. Chadjichristos12Batiment Recherche, INSERM UMR S1155, Tenon HospitalBatiment Recherche, INSERM UMR S1155, Tenon HospitalBatiment Recherche, INSERM UMR S1155, Tenon HospitalBatiment Recherche, INSERM UMR S1155, Tenon HospitalBatiment Recherche, INSERM UMR S1155, Tenon HospitalBatiment Recherche, INSERM UMR S1155, Tenon HospitalBatiment Recherche, INSERM UMR S1155, Tenon HospitalBatiment Recherche, INSERM UMR S1155, Tenon HospitalINSERM, UMR S1166, Sorbonne University, Pitié-Salpétrière HospitalINSERM, UMR S1166, Sorbonne University, Pitié-Salpétrière HospitalBatiment Recherche, INSERM UMR S1155, Tenon HospitalBatiment Recherche, INSERM UMR S1155, Tenon HospitalBatiment Recherche, INSERM UMR S1155, Tenon HospitalAbstract Background We have previously reported that the gap junction protein connexin 43 (Cx43) was upregulated in chronic renal disease in humans and rodents and plays a crucial role in the progression of experimental nephropathy. In this study, we investigated its role after renal ischemia/reperfusion (rIR), which is a major mechanism of injury in acute renal injury (AKI) and renal transplant graft dysfunction. Methods Wild-type mice (WT) and mice in which Cx43 expression was genetically reduced by half (Cx43 ±) were unilaterally nephrectomized. The left renal artery was subsequently clamped, with reperfusion of varying duration. Mice with tubular- or endothelial-specific deletion of Cx43 were also used to assess the effect of this connexin in each cell type after rIR. Kidneys were assessed for histological evaluation, immunohistochemistry, and RT-PCR. Results Blood urea nitrogen and creatininemia were progressively elevated in WT mice and picked up 48 h after rIR. At the same time point, severe tubular necrosis and dilation occurred in the cortico-medullary junction of the injured kidneys with accompanying massive neutrophil infiltration. Interestingly, Cx43 expression was progressively increased within the tubulointerstitial compartment during kidney damage progression and was paralleled closely by that of markers of renal dysfunction. Cx43 ± mice showed fewer tubular lesions, less inflammation, and further improved renal function. Similar results were observed in mice where Cx43 was specifically deleted within the vascular endothelium. In contrast, Cx43 deletion in renal tubules did not significantly improve renal structure and function after rIR. Conclusion Our findings suggest that endothelial Cx43 plays a crucial role in AKI.https://doi.org/10.1186/s10020-024-01011-6Connexin 43InflammationAcute kidney injury |
| spellingShingle | Magali Genest Satoshi Kinugasa Elena Roger Louis Boutin Sandrine Placier Stefanny Figueroa Aude Dorison Safia Hadjadj Ines Baba Emmanuel L. Gautier Panagiotis Kavvadas Christos Chatziantoniou Christos E. Chadjichristos Endothelial-specific deletion of connexin 43 improves renal function and structure after acute kidney injury Molecular Medicine Connexin 43 Inflammation Acute kidney injury |
| title | Endothelial-specific deletion of connexin 43 improves renal function and structure after acute kidney injury |
| title_full | Endothelial-specific deletion of connexin 43 improves renal function and structure after acute kidney injury |
| title_fullStr | Endothelial-specific deletion of connexin 43 improves renal function and structure after acute kidney injury |
| title_full_unstemmed | Endothelial-specific deletion of connexin 43 improves renal function and structure after acute kidney injury |
| title_short | Endothelial-specific deletion of connexin 43 improves renal function and structure after acute kidney injury |
| title_sort | endothelial specific deletion of connexin 43 improves renal function and structure after acute kidney injury |
| topic | Connexin 43 Inflammation Acute kidney injury |
| url | https://doi.org/10.1186/s10020-024-01011-6 |
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