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- Title
The VEGF Inhibitor Soluble Fms-like Tyrosine Kinase 1 Does Not Promote AKI-to-CKD Transition.
- Authors
van Aanhold, Cleo C. L.; Koudijs, Angela; Dijkstra, Kyra L.; Wolterbeek, Ron; Bruijn, Jan A.; van Kooten, Cees; Baelde, Hans J.
- Abstract
(1) Background: Soluble Fms-like tyrosine kinase 1 (sFLT1) is an endogenous VEGF inhibitor. sFLT1 has been described as an anti-inflammatory treatment for diabetic nephropathy and heart fibrosis. However, sFLT1 has also been related to peritubular capillary (PTC) loss, which promotes fibrogenesis. Here, we studied whether transfection with sFlt1 aggravates experimental AKI-to-CKD transition and whether sFLT1 is increased in human kidney fibrosis. (2) Methods: Mice were transfected via electroporation with sFlt1. After confirming transfection efficacy, mice underwent unilateral ischemia/reperfusion injury (IRI) and were sacrificed 28 days later. Kidney histology and RNA were analyzed to study renal fibrosis, PTC damage and inflammation. Renal sFLT1 mRNA expression was measured in CKD biopsies and control kidney tissue. (3) Results: sFlt1 transfection did not aggravate renal fibrosis, PTC loss or macrophage recruitment in IRI mice. In contrast, higher transfection efficiency was correlated with reduced expression of pro-fibrotic and pro-inflammatory markers. In the human samples, sFLT1 mRNA levels were similar in CKD and control kidneys and were not correlated with interstitial fibrosis or PTC loss. (4) Conclusion: As we previously found that sFLT1 has therapeutic potential in diabetic nephropathy, our findings indicate that sFLT1 can be administered at a dose that is therapeutically effective in reducing inflammation, without promoting maladaptive kidney damage.
- Subjects
VASCULAR endothelial growth factor antagonists; RENAL fibrosis; HEART fibrosis; DIABETIC nephropathies; GENE expression; PROTEIN-tyrosine kinases
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 17, p9660
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms23179660