Abstract: FR-PO326
Adam17 Inhibition Moderates Interstitial Fibrosis and Macrophage Infiltration in Type 1 Diabetes (TD1) Mouse Model
Session Information
- Diabetic Kidney Disease: Basic - I
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Riera, Marta, Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Catalunya, Spain
- Milan, Cristina Cervera, Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Catalunya, Spain
- Galdón, Eric, Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Catalunya, Spain
- Rosco, Claudia Martyn, Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Catalunya, Spain
- García, David Silva, Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Catalunya, Spain
- Fajardo, Ana Amador, Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Catalunya, Spain
- Palau, Vanesa, Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Catalunya, Spain
- Soler, Maria Jose, Hospital Universitari Vall d'Hebron, Barcelona, Catalunya, Spain
- Crespo, Marta, Hospital del Mar, Barcelona, Catalunya, Spain
- Barrios, Clara, Hospital del Mar, Barcelona, Catalunya, Spain
Group or Team Name
- GREN.
Background
ADAM17 participates in the release into circulation of inflammatory and fibrotic molecules, such as TNF-a actively involved in the progression of DN. We studied the effect of specific deletion of ADAM17 in the endothelium and renal tubule in a T1DM mouse model demonstrating its participation in the progression of kidney damage. As ADAM17 is also expressed in other cell types we will study the effect of the complete deletion of Adam17 in T1DM mouse.
Methods
We studied total inducible Adam17 knockout (ADAM17KO) male mice that were diabetic by STZ injection (DB). Glycemia, mesangial index (PAS staining), number of podocytes and positive area of a-SMA (by immunohistochemistry) were determined. We also studied the protein expression of the cytokine MCP-1 by Western Blot.
Results
The mesangial index value observed in the 20wk-DB group decreased significantly in the ADAM17KO group. Podocyte loss in DB group was not observed in the KO-DB group. For interstitial fibrosis, the intensity and location of a-SMA was significantly lower in the ADAM17KO group. In addition, the total deletion of Adam17 partly prevented the infiltration of macrophages assessed by the expression of MCP-1 in the protein extract of the renal cortex.
Conclusion
Complete inhibition of Adam17 expression in T1DM mice prevents fibrosis progression and protects the glomerulus from hypertrophy. At the same time, it reduces macrophage infiltration, limiting the inflammatory response induced by diabetes. We demonstrate the influence of Adam17 on macrophages to reduce the expression of TNF-a partly responsible for the progression of diabetic nephropathy.