Abstract: TH-PO219
Cytochrome P450: Protagonists in the Story of Diabetic Kidney Disease
Session Information
- Diabetic Kidney Disease: Basic - I
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Dia, Batoul, American University of Beirut, Beirut, Lebanon
- Shamieh, Elias, American University of Beirut, Beirut, Lebanon
- Noureldein, Mohamad, American University of Beirut, Beirut, Lebanon
- Ghadieh, Hilda E., American University of Beirut, Beirut, Lebanon
- Ziyadeh, Fuad N., American University of Beirut, Beirut, Lebanon
- Eid, Assaad Antoine, American University of Beirut, Beirut, Lebanon
Background
Diabetic kidney disease (DKD) is a debilitating complication and a major contributor to all-cause mortality in patients with diabetes. Cytochrome P450 (CYPs) epoxygenases metabolize arachidonic acid into the vasoactive and renal-active HETEs and EETs. Our group, among others, described the implication of CYPs and their metabolites in the pathogenesis of DKD by activating reactive oxygen species (ROS) production. More importantly, CYPs-encoding genes possess different polymorphisms that can alter the expression of these key enzymes, affecting the prognosis of patients with DKD. Besides, miRNAs that can be involved in DKD are recently gaining high interest. To our knowledge, the regulatory effect of miRNAs on the expression of different CYPs in DKD is not yet established. Herein, we hypothesize that in patients with diabetes, genetic variants in CYP enzymes known to be implicated in AA metabolism potentiate the development of DKD
Methods
Blood and urine were collected from healthy volunteers, patients with type 2 diabetes (T2DM) with or without clinical manifestation of DKD. Urinary and circulating levels of 20-HETE and EETs were assessed and correlated with the expression of CYPs in the kidney biopsies. Furthermore, miRNA analysis was performed to study CYP enzymes regulation
Results
Circulating levels of 20-HETE was increased in patients with DKD when compared to T2DM patients with no clinical signs of DKD, which in turn had higher levels of 20-HETE in comparison to the healthy volunteers. This was associated with an increased expression of CYP4A11 and CYP4F8 in the human kidney biopsies. In parallel, EETs levels were decreased in patients with T2DM and DKD as compared to patients with T2DM only and this was positively correlated with the decreased CYP2B6 expression in kidney biopsies. Of interest patients with DKD carry CYPs polymorph affecting their enzymatic activity and subsequently leading to increased 20-HETE and decreased EETs. The same may be concluded when it comes to our miRNA study
Conclusion
This study may yield crucial findings about novel genetic and epigenetic pathways involved in diabetes-induced renal injury and may identify novel prognostic and diagnostic biomarkers associated to CYPs pathways alteration in DKD