FGF-23 (fibroblast growth factor 23), produced by osteocytes, is a major phosphaturic hormone that acts on the kidney. Which renal effects does FGF-23 produce, and which co-receptor is required for FGF-23 signalling in the kidney?
- A FGF-23 acting with co-receptor FGFR4 increases NaPi-IIa expression to retain phosphate in states of bone turnover
- B FGF-23 acting with co-receptor klotho reduces NaPi-IIa/IIc expression in the proximal tubule (phosphaturia) and inhibits CYP27B1 (1-alpha hydroxylase), reducing 1,25(OH)2D synthesis ✓
- C FGF-23 acting with PTH receptors (PTH1R) synergistically increases phosphate reabsorption in the proximal tubule
- D FGF-23 inhibits PTH synthesis from the parathyroid gland, reducing phosphate mobilisation from bone
Explanation
FGF-23 requires klotho as its co-receptor (klotho-FGF-23-FGFR1 complex) in the proximal tubule and parathyroid gland. In the proximal tubule, FGF-23 signalling (via klotho-FGFR1 → MAPK/ERK) downregulates apical NaPi-IIa (SLC34A1) and NaPi-IIc (SLC34A3) sodiumphosphate cotransporters, increasing urinary phosphate excretion. It also inhibits CYP27B1, reducing calcitriol synthesis, and stimulates CYP24A1, enhancing vitamin D catabolism. Tumor-induced osteomalacia and X-linked hypophosphataemia involve excess FGF-23, causing severe phosphate wasting. Klotho deficiency causes a premature ageing phenotype.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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