Targeting connexin 43 protects against the progression of experimental chronic kidney disease in mice

Ahmed Abed, Julie Toubas, Panagiotis Kavvadas, Florence Authier, Dominique Cathelin, Carlo Alfieri, Jean Jacques Boffa, Jean Claude Dussaule, Christos Chatziantoniou, Christos E. Chadjichristos

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Excessive recruitment of monocytes and progression of fibrosis are hallmarks of chronic kidney disease (CKD). Recently we reported that the expression of connexin 43 (Cx43) was upregulated in the kidney during experimental nephropathy. To investigate the role of Cx43 in the progression of CKD, we interbred RenTg mice, a genetic model of hypertension-induced CKD, with Cx43+/- mice. The renal cortex of 5-month-old RenTgCx43+/- mice showed a marked decrease of cell adhesion markers leading to reduced monocyte infiltration and interstitial renal fibrosis compared with their littermates. In addition, functional and histological parameters such as albuminuria and glomerulosclerosis were ameliorated in RenTgCx43+/- mice. Interestingly, treatment with Cx43 antisense produced remarkable improvement of renal function and structure in 1-year-old RenTg mice. Similar results were found in Cx43+/- or wild-type mice treated with Cx43 antisense after obstructive nephropathy. Furthermore, in these mice, Cx43 antisense attenuated E-cadherin downregulation and phosphorylation of the transcription factor Sp1 by the ERK pathway resulting in decreased transcription of type I collagen gene. Interestingly, Cx43-specific blocking peptide inhibited monocyte adhesion in activated endothelium and profibrotic pathways in tubular cells. Cx43 was highly increased in biopsies of patients with CKD. Thus, Cx43 may represent a new therapeutic target against the progression of CKD.

Original languageEnglish
Pages (from-to)768-779
Number of pages12
JournalKidney International
Volume86
Issue number4
DOIs
Publication statusPublished - Jan 1 2014

Fingerprint

Connexin 43
Chronic Renal Insufficiency
Kidney
Monocytes
Fibrosis
Sp1 Transcription Factor
Albuminuria
MAP Kinase Signaling System
Genetic Models
Cadherins
Collagen Type I
Cell Adhesion
Endothelium
Down-Regulation
Phosphorylation
Hypertension
Biopsy

Keywords

  • chronic kidney disease
  • fibrosis
  • inflammation

ASJC Scopus subject areas

  • Nephrology
  • Medicine(all)

Cite this

Abed, A., Toubas, J., Kavvadas, P., Authier, F., Cathelin, D., Alfieri, C., ... Chadjichristos, C. E. (2014). Targeting connexin 43 protects against the progression of experimental chronic kidney disease in mice. Kidney International, 86(4), 768-779. https://doi.org/10.1038/ki.2014.108

Targeting connexin 43 protects against the progression of experimental chronic kidney disease in mice. / Abed, Ahmed; Toubas, Julie; Kavvadas, Panagiotis; Authier, Florence; Cathelin, Dominique; Alfieri, Carlo; Boffa, Jean Jacques; Dussaule, Jean Claude; Chatziantoniou, Christos; Chadjichristos, Christos E.

In: Kidney International, Vol. 86, No. 4, 01.01.2014, p. 768-779.

Research output: Contribution to journalArticle

Abed, A, Toubas, J, Kavvadas, P, Authier, F, Cathelin, D, Alfieri, C, Boffa, JJ, Dussaule, JC, Chatziantoniou, C & Chadjichristos, CE 2014, 'Targeting connexin 43 protects against the progression of experimental chronic kidney disease in mice', Kidney International, vol. 86, no. 4, pp. 768-779. https://doi.org/10.1038/ki.2014.108
Abed, Ahmed ; Toubas, Julie ; Kavvadas, Panagiotis ; Authier, Florence ; Cathelin, Dominique ; Alfieri, Carlo ; Boffa, Jean Jacques ; Dussaule, Jean Claude ; Chatziantoniou, Christos ; Chadjichristos, Christos E. / Targeting connexin 43 protects against the progression of experimental chronic kidney disease in mice. In: Kidney International. 2014 ; Vol. 86, No. 4. pp. 768-779.
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