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. 2019 Feb 21;4(4):e123817. doi: 10.1172/jci.insight.123817

Figure 2. Renal phenotypes under clamped FGF23.

Figure 2

(A) Consistent with high PTH, renal expression of 1α-hydroxylase (CYP27b1) was increased in all mice fed the adenine diet and despite the highly elevated levels of FGF23 in the flox-Fgf23/Dmp1-Cre– adenine-fed group. (B) Renal Klotho mRNA levels were reduced in the adenine-fed mice compared with the casein-fed groups. (C) Fibrosis marker Col1a1 was significantly upregulated with adenine diet administration compared with casein. These levels were maintained by 8 weeks on diet with no differences between genotypes. (D) H&E and Masson’s trichrome staining of the kidney tissue showed increased cell infiltration and fibrosis within the adenine-fed mice. Mineral accumulation detected by von Kossa staining was most pronounced in the adenine-fed flox-Fgf23/Dmp1-Cre+ group. Scale bars: 500 μm and 100 μm (insets). (E) Tnfa mRNA levels were found to be increased in both genotypes fed adenine compared with casein. Expression of inflammation markers Crp (F) and Il6 (G) mRNA was significantly induced in adenine-fed mice, but was also found at significantly higher levels in the adenine-fed flox-Fgf23/Dmp1-Cre+ mice compared with the adenine-fed flox-Fgf23/Dmp1-Cre– group. (H) Runx2 mRNA expression, related to mineral deposition, was increased in both genotypes fed adenine compared with casein (n = 4–6 per group). *P < 0.05, **P < 0.01 versus casein diet within the same genotype; ‡P < 0.05 versus Cre– on the same diet.