Effects and mechanism of fibroblast growth factor 21 on rat vascular smooth muscle cells calcification / 中华心血管病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To observe the effect and mechanism of fibroblast growth factor 21 (FGF21) on rat vascular smooth muscle cells (VSMCs) calcification in vitro.</p><p><b>METHODS</b>VSMCs was treated with calcification medium containing calcium chloride and β-glycerophosphate to induce rat VSMCs calcification in vitro. VSMCs were divided into 5 groups the control group (cultured in normal medium), the calcification group (incubated in calcified medium), the FGF21 group (cultured in calcified medium and FGF21), the PD166866 group (cultured in calcified medium and FGF21 and PD166866, inhibitor of fibroblast growth factor receptor-1 (FGFR1)), the GW9662 group (cultured in calcified medium and FGF21 and GW9662, inhibitor of peroxisome proliferators activated receptor-γ (PPAR-γ)). The calcification of VSMCs was detected by calcium content, alkaline phosphatase activity and alizarin red staining. The protein and mRNA expression of FGFR1, β-Klotho, osteocalcin and smooth muscle 22α (SM22α) were determined by western blot analysis and realtime-PCR, respectively.</p><p><b>RESULTS</b>(1) The mRNA (P < 0.01) and protein expressions of β-Klotho and FGFR1 were significantly downregulated in calcification group compared with control group (P < 0.05 or 0.01). (2) The protein levels and mRNA expression of calcium content, alkaline phosphatase activity and osteocalcin were significantly downregulated, while the protein levels and mRNA of SM22α were significantly increased in FGF21 group compared with calcification group (all P < 0.05). Moreover, alizarin red staining verified positive red nodules on calcified VSMCs was significantly reduced in FGF21 group than in calcification group. (3) Calcium content, alkaline phosphatase activity and alizarin red staining were similar between PD166866 group and calcification group (all P > 0.05). (4) Calcium content, alkaline phosphatase activity and alizarin red staining were similar between GW9662 group and calcification group (all P > 0.05).</p><p><b>CONCLUSION</b>The inhibition of VSMCs calcification by FGF21 is mediated by further downregulating FGFR1 and β-Klotho while activating PPAR-γ pathways.</p>