Human chorionic gonadotropin controls luteal vascular permeability via vascular endothelial growth factor by down regulation of a cascade of adhesion proteins

Capsule:
Junctional proteins regulate vascular permeability in the human corpus luteum. We demonstrate that vascular endothelial cadherin, nectin 2, and claudin 5 are involved in this regulation in a mutually interacting manner.

Authors:
Daniel Herr, M.D., Hamish M. Fraser, Prof. Dr., Regina Konrad, B.S., Iris Holzheu, B.S., Rolf Kreienberg, Prof. Dr., Christine Wulff, Prof. Dr.

Volume 99, Issue 6, Pages 1749-1758.e6, May 2013

Abstract:

Objective:
To study the functional interactions of junctional proteins acting as regulators of vascular permeability in the human corpus luteum. Here we investigated the role of VE-Cadherin, Nectin 2, and Claudin 5 as controllers of vascular endothelial cell permeability.

Design:
Performing immunhistochemical dual staining we co-localised the above mentioned proteins in the human corpus luteum.

Main outcome measures:
Using a granulosa-endothelial co-culture system, we revealed that hCG-treatment downregulates VE-Cadherin, Nectin 2, and Claudin 5 in endothelial cells via VEGFA.

Results:
Furthermore, the interaction of VE-Cadherin, Nectin 2, and Claudin 5 was investigated by silencing these proteins performing siRNA-knockdown. Interestingly, knockdown of VE15 Cadherin and Claudin 5 induced a decrease of the respective other protein. This downregulation was associated with changed rates of vascular permeability: hCG-induced a VEGFA-dependent downregulation of VE-Cadherin, Nectin 2, and Claudin 5 which increased the endothelial permeability in the co-culture system. Furthermore, knockdown of VE19 Cadherin, Nectin-2, and Claudin 5 also resulted in a consecutive increase of endothelial permeability for each different protein.

Conclusions:
These results demonstrate for the first time that VE-cadherin, nectin 2, and claudin 5 are involved in the regulation of vascular permeability in a mutually interacting manner, which indicates their prominent role for the functionality of the human corpus luteum.

  • Micah Hill

    Congratulations on your interesting work! I found the cell culture model you used very interesting and I would imagine culture models for the corpus luteum are a challenge and that this would be challenging to study in vivo in humans. I was curious if you had animal model studies planned to further investigate this?

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