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Connexin 43 and Pannexin 1 in Renal Cell Populations in Diabetic Kidney Disease
Marinela Jelinčić Korčulanin1, Anita Racetin1, Nikola Pavlović1
1Department of Anatomy, Histology and Embryology, University of Split School of Medicine, 21000 Split, Croatia.
Abstract:
We studied the expression of connexin 43 (Cx43) and pannexin 1 (PANX1) in different cellular populations of the kidneys of diabetic mice and diabetic and non-diabetic patients, to evaluate their role as potential therapeutic targets in diabetic kidney disease (DKD). A combination of a low dose of streptozotocin and a high-fat diet (HFD) was used to induce a type 2 diabetes model (DM2) in mice. Kidney tissues from diabetic (n = 9) and control patients (n = 11) who underwent nephrectomy were collected. Tissues from mice and humans were processed for double immunofluorescence, using antibodies against Cx43, phosphorylated Cx43 (pCx43) or PANX1 and markers for specific cell populations: endothelium (CD31/PECAM1); pericytes/mesangium (PDGFRB); podocytes (nephrin/synaptopodin); proximal tubules and collecting ducts (aquaporin 2). The results showed a significant decrease in the expression of pCx43 in PDGFRB-immunoreactive mesangium in diabetic patients compared to the control group (p < 0.0001). This contrasted with an increase in pCx43 in pericytes of diabetic mice (p = 0.1). However, we found a general decrease in Cx43 protein expression in diabetic mouse kidneys (p < 0.05). We also found a decrease in the expression of PANX1 in endothelial cells of diabetic patients (p < 0.05) and a significant increase in PANX1 expression in cells expressing PDGFRB (p < 0.05). Expression of PANX1 in endothelium (r = -0.50; p < 0.05) and pCx43 in the mesangium (r = -0.65; p < 0.01) correlated negatively with the percentage of sclerotic glomeruli. The expression and activation of Cx43 and the expression of PANX1 are altered in distinct populations of renal cells during long-term type 2 diabetes mellitus, especially cells of the vascular wall. This may indicate their role in the pathophysiological processes of DKD. Therefore, connexin and pannexin channels could be considered as possible therapeutic targets in the prevention and treatment of diabetic kidney disease.
Insights
Diabetic kidney disease involves altered expression of connexin 43 (Cx43) and pannexin 1 (PANX1) in kidney cells. These channels may be therapeutic targets for preventing and treating diabetic kidney disease.
Area of Science:
- Nephrology
- Cell Biology
- Molecular Medicine
Background:
- Diabetic kidney disease (DKD) is a major complication of diabetes.
- Connexin 43 (Cx43) and pannexin 1 (PANX1) are implicated in cellular communication and disease pathogenesis.
- Understanding their role in DKD is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the expression and activation of Cx43 and PANX1 in specific renal cell populations in diabetic conditions.
- To evaluate Cx43 and PANX1 as potential therapeutic targets for DKD.
Main Methods:
- A type 2 diabetes model was induced in mice using streptozotocin and a high-fat diet.
- Kidney tissues from diabetic and control mice, and diabetic and non-diabetic patients were analyzed.
- Double immunofluorescence was employed using cell-specific markers and antibodies against Cx43, phosphorylated Cx43 (pCx43), and PANX1.
Main Results:
- A significant decrease in pCx43 was observed in the mesangium of diabetic patients.
- Cx43 protein expression generally decreased in diabetic mouse kidneys.
- PANX1 expression decreased in endothelial cells but increased in PDGFRB-expressing cells of diabetic patients.
- PANX1 and pCx43 expression correlated negatively with glomerular sclerosis.
Conclusions:
- Cx43 and PANX1 expression and activation are altered in renal cells, particularly vascular cells, in type 2 diabetes.
- These alterations suggest a role for Cx43 and PANX1 in DKD pathogenesis.
- Connexin and pannexin channels represent potential therapeutic targets for DKD prevention and treatment.
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