Figures & data
Figure 1. DOCA salt induced a significant increase in the synthesis and secretion of FGF21. The male C57BL/6 mice were subjected to uninephrectomy with or without deoxycorticosterone acetate (DOCA)-salt treatment for 6 weeks. (a) Plasma FGF21 was measured by immunoassay. (b) FGF21 mRNA levels in liver and PVN and (c) FGF21 protein expression levels in liver were examined by real-time qPCR and western-blot, respectively. Data were expressed as the means ± SD (n=5/group). *p<0.05 vs others.
Figure 2. FGF21 intervention reduced DOCA salt-induced sympathetic activation and hypertension. The male C57BL/6 mice were subjected to uninephrectomy with or without deoxycorticosterone acetate (DOCA)-salt treatment for 6 weeks. At the same time, the mice were infused with vehicle (artificial cerebrospinal fluid, aCSF, 0.4 μL/h) or FGF21 (1 mg/kg, 0.4 μL/h) into the bilateral PVN of mice for 6 weeks. (a) Heart rate was measured by tail-cuff plethysmography. (b) NE level in plasma was measured by ELISA kits. (c) Systolic blood pressure (SBP) was measured by tail-cuff plethysmography. Data were expressed as the means ± SD (n=5/group). *p<0.05 vs others.
Figure 3. FGF21 intervention lowered DOCA salt-induced inflammation and oxidative stress in the PVN. The male C57BL/6 mice were subjected to uninephrectomy with or without deoxycorticosterone acetate (DOCA)-salt treatment for 6 weeks. At the same time, the mice were infused with vehicle (artificial cerebrospinal fluid, aCSF, 0.4 μL/h) or FGF21 (1 mg/kg, 0.4 μL/h) into the bilateral PVN of mice for 6 weeks. (a and b) inflammatory markers including TNF-α and IL-6 in the PVN were measured by ELISA kits. (c and d) oxidative stress markers including MDA and GSH in the PVN were measured by ELISA kits. Data were expressed as the means ± SD (n=5/group). *p<0.05 vs others.
Figure 4. The role of HNF4α/ACE2/Ang (1–7) signaling in antihypertensive function of FGF21. The male C57BL/6 mice were subjected to uninephrectomy with or without deoxycorticosterone acetate (DOCA)-salt treatment for 6 weeks. At the same time, the mice were infused with vehicle (artificial cerebrospinal fluid, aCSF, 0.4 μL/h) or FGF21 (1 mg/kg, 0.4 μL/h) into the bilateral PVN of mice for 6 weeks. (a) ACE2 expression was measured by western-blot. (b) Ang (1–7) levels in the PVN were measured by immunoassay. (c and d) HNF4α expression and the binding activity of HNF4α to the ACE2 promoter region were measured by western-blot and CHIP assay, respectively. Data were expressed as the means ± SD (n=5/group). *p<0.05 vs others.
Figure 5. ACE2 deficiency abolished the protective effect of FGF21 in DOCA salt-induced hypertension. ACE2 deficiency and WT mice were subjected to uninephrectomy with deoxycorticosterone acetate (DOCA)-salt treatment for 6 weeks. At the same time, the mice were infused with vehicle (artificial cerebrospinal fluid, aCSF, 0.4 μL/h) or FGF21 (1 mg/kg, 0.4 μL/h) into the bilateral PVN of mice for 6 weeks. (a) Ang (1–7) levels in the PVN were measured by immunoassay. (b) Heart rate was measured by tail-cuff plethysmography. (c) NE level in plasma was measured by ELISA kits. (d) SBP was measured by tail-cuff plethysmography at the age of 16 weeks. Data were expressed as the means ± SD (n=5/group). *p<0.05 vs WT mice, #p<0.05 vs WT+FGF21 group.
