scholarly journals Acute Kidney Injury Sensitizes the Brain Vasculature to Ang II (Angiotensin II) Constriction via FGFBP1 (Fibroblast Growth Factor Binding Protein 1)

Hypertension ◽  
2020 ◽  
Vol 76 (6) ◽  
pp. 1924-1934
Author(s):  
Liang Zhao ◽  
Xiaoyun Cao ◽  
Lingli Li ◽  
Xiaohua Wang ◽  
Qin Wang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Angiotensin Ii ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Kidney Injury ◽  
Fibroblast Growth ◽  
Ang Ii ◽  
Brain Vessels ◽  
Vessel Injury ◽  
Brain Vessel

Acute kidney injury (AKI) causes multiple organ dysfunction. Here, we identify a possible mechanism that can drive brain vessel injury after AKI. We induced 30-minute bilateral renal ischemia-reperfusion injury in C57Bl/6 mice and isolated brain microvessels and macrovessels 24 hours or 1 week later to test their responses to vasoconstrictors and found that after AKI brain vessels were sensitized to Ang II (angiotensin II). Upregulation of FGF2 (fibroblast growth factor 2) and FGFBP1 (FGF binding protein 1) expression in both serum and kidney tissue after AKI suggested a potential contribution to the vascular sensitization. Administration of FGF2 and FGFBP1 proteins to isolated healthy brain vessels mimicked the sensitization to Ang II after AKI. Brain vessels in Fgfbp1 −/− AKI mice failed to induce Ang II sensitization. Complementary to this, systemic treatment with the clinically used FGF receptor kinase inhibitor BGJ398 (Infigratinib) reversed the AKI-induced brain vascular sensitization to Ang II. All these findings lead to the conclusion that FGFBP1 is especially necessary for AKI-mediated brain vascular sensitization to Ang II and inhibitors of FGFR pathway may be beneficial in preventing AKI-induced brain vessel injury.

scholarly journals Effects of acute kidney injury and chronic hypoxemia on fibroblast growth factor 23 levels in pediatric cardiac surgery patients

2015 ◽  
Vol 31 (4) ◽  
pp. 661-669 ◽  
Author(s):  
Mark R. Hanudel ◽  
Katherine Wesseling-Perry ◽  
Barbara Gales ◽  
Georgina Ramos ◽  
Vicky Campbell ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Cardiac Surgery ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Kidney Injury ◽  
Pediatric Cardiac Surgery ◽  
Fibroblast Growth ◽  
Chronic Hypoxemia

Erythropoietin induces bone marrow and plasma fibroblast growth factor 23 during acute kidney injury

2018 ◽  
Vol 93 (5) ◽  
pp. 1131-1141 ◽  
Author(s):  
Luis Toro ◽  
Víctor Barrientos ◽  
Pablo León ◽  
Macarena Rojas ◽  
Magdalena Gonzalez ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Kidney Injury ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Kidney Injury ◽  
Fibroblast Growth

scholarly journals Role of circulating fibroblast growth factor-2 in lipopolysaccharide-induced acute kidney injury in mice

2011 ◽  
Vol 27 (3) ◽  
pp. 469-483 ◽  
Author(s):  
Parnell C. Mattison ◽  
Ángel A. Soler-García ◽  
Jharna R. Das ◽  
Marina Jerebtsova ◽  
Sofia Perazzo ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Kidney Injury ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth

scholarly journals Fibroblast Growth Factor 23 Regulation and Acute Kidney Injury

Nephron ◽  
2021 ◽  
pp. 1-4
Author(s):  
Wen Zhou ◽  
Petra Simic ◽  
Eugene P. Rhee
Keyword(s):  
Bone Marrow ◽  
Acute Kidney Injury ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Human Subjects ◽  
Fibroblast Growth Factor 23 ◽  
Kidney Injury ◽  
Adverse Outcomes ◽  
Fibroblast Growth ◽  
Signaling Axis

Elevated fibroblast growth factor 23 (FGF23) levels are markers and potential mediators, of adverse outcomes in acute kidney injury (AKI). We recently identified glycerol-3-phosphate (G-3-P), a glycolysis byproduct, as a kidney-derived factor that circulates to bone and bone marrow and triggers FGF23 production in ischemic AKI. This kidney-to-bone signaling axis was further shown to require the conversion of G-3-P to lysophosphatidic acid (LPA) in bone marrow, followed by LPA signaling through the LPAR1 receptor. These findings highlight discrete steps potentially amenable to therapeutic targeting in conditions of FGF23 excess, although more work is required to determine the specificity and safety of targeting specific enzyme and receptor isoforms. Importantly, the initial metabolomic screen that identified a strong correlation between renal vein G-3-P and circulating FGF23 was conducted in human subjects undergoing elective catheterization, none with AKI. This raises the question of whether G-3-P might also modulate FGF23 homeostasis in patients with more mild or chronic decrements in kidney function, or under normal physiologic conditions – a question that is reinforced by a growing body of literature highlighting functional roles for a range of circulating metabolites traditionally thought to function exclusively inside cells.

scholarly journals Fibroblast Growth Factor 23 and αKlotho in Acute Kidney Injury: Current Status in Diagnostic and Therapeutic Applications

Nephron ◽  
2020 ◽  
Vol 144 (12) ◽  
pp. 665-672
Author(s):  
Javier A. Neyra ◽  
Ming Chang Hu ◽  
Orson W. Moe
Keyword(s):  
Acute Kidney Injury ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Kidney Injury ◽  
Current Status ◽  
Fibroblast Growth ◽  
Diverse Range ◽  
Association Data ◽  
Fgf 23

Fibroblast growth factor (FGF) 23 and αKlotho are circulating mineral regulatory substances that also have a very diverse range of actions. Acute kidney injury (AKI) is a state of high FGF23 and low αKlotho. Clinical association data for FGF23 are strong, but the basic pathobiology of FGF23 in AKI is rather sparse. Conversely, preclinical data supporting a pathogenic role of αKlotho in AKI are strong, but the human data are still being generated. This pair of substances can potentially serve as diagnostic and prognostic biomarkers. FGF23 blockade and αKlotho restoration can have prophylactic and therapeutic utility in AKI. The literature to date is briefly reviewed in this article.

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