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Author L Darryl Quarles

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FGF-23 Deficiency Impairs Hippocampal-Dependent Cognitive Function.

Ann M Laszczyk, Dailey Nettles, Tate A Pollock, Stephanie Fox, Melissa L Garcia, Jing Wang, L Darryl Quarles, Gwendalyn D King,

Fibroblast growth factor receptor (FGFR) and α-Klotho transduce FGF-23 signaling in renal tubules to maintain systemic phosphate/vitamin D homeostasis. Mice deficient for either the ligand, FGF-23, or the co-receptor, Klotho, are phenocopies with both showing rapid and premature development of multiple aging-like abnormalities. Such similarity in phenotype, suggests that FGF-23 ... Read more >>

eNeuro (eNeuro)
[2019, 6(2):]

Cited: 0 times

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Human GPRC6A Mediates Testosterone-Induced Mitogen-Activated Protein Kinases and mTORC1 Signaling in Prostate Cancer Cells.

Ruisong Ye, Min Pi, Mohammed M Nooh, Suleiman W Bahout, L Darryl Quarles,

G protein-coupled receptor family C group 6 member A (GPRC6A) is activated by testosterone and modulates prostate cancer progression. Most humans have a GPRC6A variant that contains a recently evolved KGKY insertion/deletion in the third intracellular loop (ICL3) (designated as GPRC6AICL3_KGKY) that replaces the ancestral KGRKLP sequence (GPRC6AICL3_RKLP) present in ... Read more >>

Mol. Pharmacol. (Molecular pharmacology)
[2019, 95(5):563-572]

Cited: 0 times

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Fibroblast growth factor 23 and α-Klotho co-dependent and independent functions.

L Darryl Quarles,

PURPOSE OF REVIEW:The current review examines what is known about the FGF-23/α-Klotho co-dependent and independent pathophysiological effects, and whether FGF-23 and/or α-Klotho are potential therapeutic targets. RECENT FINDINGS:FGF-23 is a hormone derived mainly from bone, and α-Klotho is a transmembrane protein. Together they form a trimeric signaling complex with FGFRs ... Read more >>

Curr. Opin. Nephrol. Hypertens. (Current opinion in nephrology and hypertension)
[2019, 28(1):16-25]

Cited: 1 time

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Validation of a Novel Modified Aptamer-Based Array Proteomic Platform in Patients with End-Stage Renal Disease.

Zhongji Han, Zhousheng Xiao, Kamyar Kalantar-Zadeh, Hamid Moradi, Tariq Shafi, Sushrut S Waikar, L Darryl Quarles, Zhi Yu, Adrienne Tin, Josef Coresh, Csaba P Kovesdy,

End stage renal disease (ESRD) is characterized by complex metabolic abnormalities, yet the clinical relevance of specific biomarkers remains unclear. The development of multiplex diagnostic platforms is creating opportunities to develop novel diagnostic and therapeutic approaches. SOMAscan is an innovative multiplex proteomic platform which can measure >1300 proteins. In the ... Read more >>

Diagnostics (Basel) (Diagnostics (Basel, Switzerland))
[2018, 8(4):]

Cited: 0 times

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Letter to the Editor: "Increased Circulating FGF23 Does Not Lead to Cardiac Hypertrophy in the Male Hyp Mouse Model of XLH".

Xiaobin Han, L Darryl Quarles,

Endocrinology (Endocrinology)
[2018, 159(11):3655-3656]

Cited: 0 times

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Cardiovascular Interactions between Fibroblast Growth Factor-23 and Angiotensin II.

Min Pi, Ruisong Ye, Xiaobin Han, Benjamin Armstrong, Xue Liu, Yuanjian Chen, Yao Sun, L Darryl Quarles,

Both the activation of the renin angiotensin aldosterone system (RAAS) and elevations of circulating Fibroblast Growth Factor-23 (FGF-23) have been implicated in the pathogenesis of left ventricular hypertrophy (LVH) in chronic kidney disease. To investigate potential cross-talk between RAAS and FGF-23, we administered angiotensin II (Ang II) to wild-type rodents ... Read more >>

Sci Rep (Scientific reports)
[2018, 8(1):12398]

Cited: 3 times

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Role of Fibroblast Growth Factor-23 in Innate Immune Responses.

Elizabeth A Fitzpatrick, Xiaobin Han, Zhousheng Xiao, L Darryl Quarles,

Fibroblast growth factor-23 (FGF-23) is a bone-derived hormone that activates FGFR/α-Klotho binary complexes in the kidney renal tubules to regulate phosphate reabsorption and vitamin D metabolism. The objective of this review is to discuss the emerging data that show that FGF-23 has functions beyond regulation of mineral metabolism, including roles ... Read more >>

Front Endocrinol (Lausanne) (Frontiers in endocrinology)
[2018, 9:320]

Cited: 1 time

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Changes With Lanthanum Carbonate, Calcium Acetate, and Phosphorus Restriction in CKD: A Randomized Controlled Trial.

Csaba P Kovesdy, Jun Ling Lu, Barry M Wall, Geeta Gyamlani, Adnan Naseer, Angela Wallick, Zhongji Han, Fridtjof Thomas, L Darryl Quarles, Nabil Jarmukli,

Abnormal phosphorus homeostasis develops early in chronic kidney disease (CKD). It is unclear if its correction results in improved clinical outcomes in non-dialysis dependent CKD.We conducted a randomized controlled, parallel design clinical trial in 120 patients with estimated glomerular filtration rate 15 to 59 ml/min per 1.73 m2 and abnormal ... Read more >>

Kidney Int Rep (Kidney international reports)
[2018, 3(4):897-904]

Cited: 1 time

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Polycystin-1 interacts with TAZ to stimulate osteoblastogenesis and inhibit adipogenesis.

Zhousheng Xiao, Jerome Baudry, Li Cao, Jinsong Huang, Hao Chen, Charles R Yates, Wei Li, Brittany Dong, Christopher M Waters, Jeremy C Smith, L Darryl Quarles,

The molecular mechanisms that transduce the osteoblast response to physical forces in the bone microenvironment are poorly understood. Here, we used genetic and pharmacological experiments to determine whether the polycystins PC1 and PC2 (encoded by Pkd1 and Pkd2) and the transcriptional coactivator TAZ form a mechanosensing complex in osteoblasts. Compound-heterozygous ... Read more >>

J. Clin. Invest. (The Journal of clinical investigation)
[2018, 128(1):157-174]

Cited: 9 times

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Cardiovascular Effects of Renal Distal Tubule Deletion of the FGF Receptor 1 Gene.

Xiaobin Han, Jed Ross, Ganesh Kolumam, Min Pi, Junichiro Sonoda, Gwendalyn King, L Darryl Quarles,

The bone-derived hormone fibroblast growth factor-23 (FGF-23) activates complexes composed of FGF receptors (FGFRs), including FGFR1, and α-Klotho in the kidney distal tubule (DT), leading to increased sodium retention and hypertension. However, the role of FGFR1 in regulating renal processes linked to hypertension is unclear. Here, we investigated the effects ... Read more >>

J. Am. Soc. Nephrol. (Journal of the American Society of Nephrology : JASN)
[2018, 29(1):69-80]

Cited: 6 times

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CRISPR/Cas9 targeting of GPRC6A suppresses prostate cancer tumorigenesis in a human xenograft model.

Ruisong Ye, Min Pi, John V Cox, Satoru K Nishimoto, L Darryl Quarles,

GPRC6A is implicated in the pathogenesis of prostate cancer, but its role remains uncertain because of a purported tolerant gene variant created by substitution of a K..Y polymorphism in the 3rd intracellular loop (IL) that evolved in the majority of humans and replaces the ancestral RKLP present in 40% of ... Read more >>

J. Exp. Clin. Cancer Res. (Journal of experimental & clinical cancer research : CR)
[2017, 36(1):90]

Cited: 5 times

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GPRC6A: Jack of all metabolism (or master of none).

Min Pi, Satoru Kenneth Nishimoto, L Darryl Quarles,

BACKGROUND:GPRC6A, a widely expressed G-protein coupled receptor, is proposed to be a master regulator of complex endocrine networks and metabolic processes. GPRC6A is activated by multiple ligands, including osteocalcin (Ocn), testosterone (T), basic amino acids, and various cations. SCOPE OF REVIEW:We review the controversy surrounding GPRC6A functions. In mice, GPRC6A ... Read more >>

Mol Metab (Molecular metabolism)
[2017, 6(2):185-193]

Cited: 8 times

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The hypoxia-inducible factor-1α activates ectopic production of fibroblast growth factor 23 in tumor-induced osteomalacia.

Qian Zhang, Michele Doucet, Ryan E Tomlinson, Xiaobin Han, L Darryl Quarles, Michael T Collins, Thomas L Clemens,

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome in which ectopic production of fibroblast growth factor 23 (FGF23) by non-malignant mesenchymal tumors causes phosphate wasting and bone fractures. Recent studies have implicated the hypoxia-inducible factor-1α (HIF-1α) in other phosphate wasting disorders caused by elevated FGF23, including X-linked hypophosphatemic rickets and ... Read more >>

Bone Res (Bone research)
[2016, 4:16011]

Cited: 13 times

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Multiple faces of fibroblast growth factor-23.

Xiaobin Han, L Darryl Quarles,

This review examines the role of fibroblast growth factor-23 (FGF-23) in mineral metabolism, innate immunity and adverse cardiovascular outcomes.FGF-23, produced by osteocytes in bone, activates FGFR/α-Klotho (α-Kl) complexes in the kidney. The resulting bone-kidney axis coordinates renal phosphate reabsorption with bone mineralization, and creates a counter-regulatory feedback loop to prevent ... Read more >>

Curr. Opin. Nephrol. Hypertens. (Current opinion in nephrology and hypertension)
[2016, 25(4):333-342]

Cited: 7 times

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Conditional Deletion of Fgfr1 in the Proximal and Distal Tubule Identifies Distinct Roles in Phosphate and Calcium Transport.

Xiaobin Han, Jiancheng Yang, Linqiang Li, Jinsong Huang, Gwendalyn King, L Darryl Quarles,

A postnatal role of fibroblast growth factor receptor-1 (FGFR1) in the kidney is suggested by its binding to α-Klotho to form an obligate receptor for the hormone fibroblast growth factor-23 (FGF-23). FGFR1 is expressed in both the proximal and distal renal tubular segments, but its tubular specific functions are unclear. ... Read more >>

PLoS ONE (PloS one)
[2016, 11(2):e0147845]

Cited: 15 times

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FGF23 from bench to bedside.

Csaba P Kovesdy, L Darryl Quarles,

There is a strong association between elevated circulating fibroblast growth factor-23 (FGF23) levels and adverse outcomes in patients with chronic kidney disease (CKD) of all stages. Initially discovered as a regulator of phosphate and vitamin D homeostasis, FGF23 has now been implicated in several pathophysiological mechanisms that may negatively impact ... Read more >>

Am. J. Physiol. Renal Physiol. (American journal of physiology. Renal physiology)
[2016, 310(11):F1168-74]

Cited: 22 times

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Enhanced FGF23 production in mice expressing PI3K-insensitive GSK3 is normalized by β-blocker treatment.

Abul Fajol, Hong Chen, Anja T Umbach, L Darryl Quarles, Florian Lang, Michael Föller,

Glycogen synthase kinase (GSK)-3 is a ubiquitously expressed kinase inhibited by insulin-dependent Akt/PKB/SGK. Mice expressing Akt/PKB/SGK-resistant GSK3α/GSK3β (gsk3(KI)) exhibit enhanced sympathetic nervous activity and phosphaturia with decreased bone density. Hormones participating in phosphate homeostasis include fibroblast growth factor (FGF)-23, a bone-derived hormone that inhibits 1,25-dihydroxyvitamin D3 (1,25(OH)2D3; calcitriol) formation and ... Read more >>

FASEB J. (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2016, 30(2):994-1001]

Cited: 12 times

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Membrane and integrative nuclear fibroblastic growth factor receptor (FGFR) regulation of FGF-23.

Xiaobin Han, Zhousheng Xiao, L Darryl Quarles,

J. Biol. Chem. (The Journal of biological chemistry)
[2015, 290(33):20101]

Cited: 6 times

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Structural and Functional Evidence for Testosterone Activation of GPRC6A in Peripheral Tissues.

Min Pi, Karan Kapoor, Yunpeng Wu, Ruisong Ye, Susan E Senogles, Satoru K Nishimoto, Dong-Jin Hwang, Duane D Miller, Ramesh Narayanan, Jeremy C Smith, Jerome Baudry, L Darryl Quarles,

G protein-coupled receptor (GPCR) family C group 6 member A (GPRC6A) is a multiligand GPCR that is activated by cations, L-amino acids, and osteocalcin. GPRC6A plays an important role in the regulation of testosterone (T) production and energy metabolism in mice. T has rapid, transcription-independent (nongenomic) effects that are mediated ... Read more >>

Mol. Endocrinol. (Molecular endocrinology (Baltimore, Md.))
[2015, 29(12):1759-1773]

Cited: 12 times

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Membrane and integrative nuclear fibroblastic growth factor receptor (FGFR) regulation of FGF-23.

Xiaobin Han, Zhousheng Xiao, L Darryl Quarles,

Fibroblastic growth factor receptor 1 (FGFR1) signaling pathways are implicated in the regulation of FGF-23 gene transcription, but the molecular pathways remain poorly defined. We used low molecular weight (LMW, 18 kDa) FGF-2 and high molecular weight (HMW) FGF-2 isoforms, which, respectively, activate cell surface FGF receptors and intranuclear FGFR1, ... Read more >>

J. Biol. Chem. (The Journal of biological chemistry)
[2015, 290(16):10447-10459]

Cited: 15 times

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Activation of FGF-23 mediated vitamin D degradative pathways by cholecalciferol.

Hala Alshayeb, Arif Showkat, Barry M Wall, Geeta G Gyamlani, Valentin David, L Darryl Quarles,

The optimal circulating concentration of 25(OH) vitamin D is controversial.The aim was to investigate if FGF-23 and 24,25(OH)2D can guide cholecalciferol replacement.Oral cholecalciferol (10,000 IU weekly) administered to subjects with 25(OH)D levels < 20 ηg/mL and eGFR > 60 mL/min/1.73 m(2) (n = 25), chronic kidney disease (CKD) (n = ... Read more >>

J. Clin. Endocrinol. Metab. (The Journal of clinical endocrinology and metabolism)
[2014, 99(10):E1830-7]

Cited: 9 times

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Association of body mass index with outcomes in patients with CKD.

Jun Ling Lu, Kamyar Kalantar-Zadeh, Jennie Z Ma, L Darryl Quarles, Csaba P Kovesdy,

Obesity is associated with higher mortality in the general population, but this association is reversed in patients on dialysis. The nature of the relationship of obesity with adverse clinical outcomes in nondialysis-dependent CKD and the putative interaction of the severity of disease with this association are unclear. We analyzed data ... Read more >>

J. Am. Soc. Nephrol. (Journal of the American Society of Nephrology : JASN)
[2014, 25(9):2088-2096]

Cited: 76 times

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Novel bone endocrine networks integrating mineral and energy metabolism.

Min Pi, L Darryl Quarles,

The skeleton is an endocrine organ that regulates energy metabolism through the release of the osteoblast-derived hormone, osteocalcin (Ocn), and phosphate and vitamin D homeostasis through the secretion by osteoblasts and osteocytes of the novel hormone, FGF23 Ocn activates a widely expressed G-protein coupled receptor, GPRC6A, to regulate insulin secretion ... Read more >>

Curr Osteoporos Rep (Current osteoporosis reports)
[2013, 11(4):391-399]

Cited: 19 times

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Calcium regulates FGF-23 expression in bone.

Valentin David, Bing Dai, Aline Martin, Jinsong Huang, Xiaobin Han, L Darryl Quarles,

Calcium has recently been shown to regulate fibroblast growth factor 23 (FGF-23), a bone-derived phosphate and vitamin D-regulating hormone. To better understand the regulation of FGF-23 by calcium, phosphorus, 1,25 dihydroxyvitamin D3 [1,25(OH)2D], and PTH, we examined FGF-23 expression under basal conditions and in response to PTH, doxercalciferol, or high-calcium ... Read more >>

Endocrinology (Endocrinology)
[2013, 154(12):4469-4482]

Cited: 52 times

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Blood pressure and mortality in U.S. veterans with chronic kidney disease: a cohort study.

Csaba P Kovesdy, Anthony J Bleyer, Miklos Z Molnar, Jennie Z Ma, John J Sim, William C Cushman, L Darryl Quarles, Kamyar Kalantar-Zadeh,

The ideal blood pressure (BP) to decrease mortality rates in patients with non-dialysis-dependent chronic kidney disease (CKD) is unclear.To assess the association of BP (defined as the combination of systolic BP [SBP] and diastolic BP [DBP] at the individual level) with death in patients with CKD.Historical cohort between 2005 and ... Read more >>

Ann. Intern. Med. (Annals of internal medicine)
[2013, 159(4):233-242]

Cited: 95 times

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