Abstract: FR-PO135
Integrin-Linked Kinase Depletion Prevents Fibrosis and the Decrease of Mitochondrial Complex Functionality in Folic Acid-Induced Nephropathy
Session Information
- AKI: Mechanisms - II
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Campillo de Blas, Sofia, Department of Systems Biology, Physiology Unit, Universidad de Alcalá, Alcalá de Henares (Madrid), Madrid, Spain
- de la Serna, Mariano, NOVELREN, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Fundación Renal Iñigo Álvarez de Toledo (FRIAT) and REDinREN, (ISCIII), Alcalá de Henares (Madrid), Madrid, Spain
- Gutierrez Calabres, Elena, Department of Systems Biology, Physiology Unit, Universidad de Alcalá, Alcalá de Henares (Madrid), Madrid, Spain
- Canales Bueno, Natalia, NOVELREN, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Fundación Renal Iñigo Álvarez de Toledo (FRIAT) and REDinREN, (ISCIII), Alcalá de Henares (Madrid), Madrid, Spain
- González Valero, Cristina, NOVELREN, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Fundación Renal Iñigo Álvarez de Toledo (FRIAT) and REDinREN, (ISCIII), Alcalá de Henares (Madrid), Madrid, Spain
- Griera, Mercedes, Department of Systems Biology, Physiology Unit, Universidad de Alcalá. Graphenano Medical Care S.L., Alcalá de Henares (Madrid), Madrid, Spain
- De frutos garcia, Sergio, Department of Systems Biology, Physiology Unit, Universidad de Alcalá. Graphenano Medical Care S.L., Alcalá de Henares (Madrid), Madrid, Spain
- Calleros, Laura, Department of Systems Biology, Physiology Unit, Universidad de Alcalá, Alcalá de Henares (Madrid), Madrid, Spain
- Rodriguez puyol, Diego, Nephrology Unit, Hospital Universitario Príncipe de Asturias, Department of Medicine and Medical Specialties and Graphenano Medical Care S.L., Alcalá de Henares (Madrid), Madrid, Spain
Background
Integrin-linked kinase (ILK), a major scaffold protein between the extracellular matrix and intracellular signaling pathways, is involved in several pathophysiological processes during renal damage. There are few studies on the mitochondrial dysfunction that occurs after renal failure in the Folic Acid-induced nephropathy (FA). The aim of this work was to study the role of ILK in renal interstitial fibrosis associated with mitochondrial dysfunction that appears during acute kidney injury (AKI) to chronic kidney disease (CKD) transition induced by FA administration.
Methods
Males of the C57BL/6 WT strain and adult conditional ILK knock-down (cKD-ILK) were injected intraperitoneally with a single dose of FA (250 mg/Kg) dissolved in Sodium Bicarbonate (0.3 mmol/L), with sacrifice at 15 days. We determined the expression of ILK, extracellular matrix protein (Fibronectin: FN and Collagen type I: COL1A1), the profibrotic cytokine TGF-β1 and the mitochondrial electron transport chain complexes (COXI: NADPH DH, COXII: Succinate DH, COXIII: Coenzyme Q, COXIV: Cytochrome C Oxidase and COXV: ATP Synthase) by Western Blot and COXIV activity by colorimetric assay kit in the mice renal cortex.
Results
ILK expression increases in the renal cortex of FA treated WT mice, which does not occur in the cKD-ILK FA group. Moreover, we observed an increase of fibrotic markers (FN, COL1A1) and TGF-β in the WT FA group, which was significantly lower in FA cKD-ILK mice. Regarding the complexes of the mitochondria, we observed a notable protein decrease of these complexes in the WT FA group and the protein content of COXI and COXIV that was partly recovered after ILK deletion (as also occurs with COXIV activity). Positive correlations with ILK expression levels were obtained for all studied markers.
Conclusion
These data suggest that ILK plays a relevant role in the renal fibrosis development and mitochondrial dysfunction after FA-induced AKI-CKD transition, since its deletion prevents fibrosis and improves mitochondrial dysfunction. Further studies will be aimed to elucidate the underlying mechanism between ILK, mitochondrial dysfunction and fibrosis.
Funding
- Other NIH Support