Disorder Of ERK1/2Phosphorylation Pathway In The Pathogenesis Of Secondary Hyperparathyroidism Resulted From Chronic Renal Failure

BackgroundSecondary hyperparathyroidism (SHPT) was a common complication of chronic renal failure (CRF). Patients often suffer irreversible damage of multiple systems due to high level of parathyroid hormone (PTH) and metabolic disturbance of calcium and phosphorus, which seriously influence patients’ life quality. The pathogenesis of SHPT is associated with various of factors, among them, the pathway that factor receptor expression-23(FGF-23) regulates PTH may play an important role. Under physiological condition, FGF-23combines to Klotho-Fibroblast growth factor receptor-1(FGFR-1) on parathyroid gland cell membrane, transfers signal into cells and actives extracellular regulated protein kinasesl/2(ERK1/2) signal transduction pathway to inhibit secretion of PTH.ObjectiveOur study aims to investigate the role of ERK1/2signal transduction pathway in the pathogenesis of SHPT by detecting level of serum FGF-23, PTH and expression of ERKl/2, p-ERKl/2, the Early growth response-1(Egr-1) in parathyroid cell.Methods1. Patient population8male cadaver with normal kidney function were selected as control group. A total of50SHPT patients,33males and17females, were selected as SHPT group. All of them were accepted parathyroideetomy(PTX).2. MethodsBlood samples and parathyroid tissue specimens were collected.(1) Biochemical marker detection:Detect levels of serum Ca, P, ALP and PTH.(2) Serum FGF-23:Serum FGF-23was detected by enzyme-linked immunosorbent assay (ELISA).(3)Immunohistochemistry:Parathyroid tissue specimens were dealt with hematoxylin-eosin staining (HE). The expression of ERK1/2、p-ERK1/2、Egr-1were detected by immunohistochemistry. Observe positive cells with light microscope, and count the average rate of positive cells.3. Statistic analysisData was analysed by the SPSS18.0software. All values were expressed as means±SD (x±s). Statistical significance was determined by variance analysis.Pearson’s correlation analyses were used to examine relationships between each parameter. It was considered statistically significant when P<0.05.Results1. In SHPT group, serum FGF-23was positively correlated with PTH (r=0.438, P<0.05), serum P (r=0.421, P<0.05) and ALP (r=0.452, P<0.05), and there was no relationship between FGF-23and serum Ca (P>0.05)2. Compared with FGF-23pre-parathyroidectomy, the FGF-23level significantly decreased in SHPT group post-parathyroidectomy (P<0.05)3. Compared with control group, the expression of ERK1/2in SHPT group had no difference (P>0.05), the expression of p-ERK1/2and Egr-1in SHPT group decreased significantly (P<0.05). Compared with diffusible hyperplasia group, the expression of p-ERK1/2and Egr-1in adenoma hyperplasia group decreased significantly (P<0.05)4. In SHPT group, serum PTH was negatively correlated with the expression of ERK1/2 (r=-0.656, P<0.05),p-ERK1/2(r=-0.696, P<0.05), Egr-1(r=-0.439, P<0.05) in parathyroid cells. FGF-23was negatively correlated with the expression of ERK1/2(r=-0.565, P<0.05), p-ERK1/2(r=-0.453, P<0.05), Egr-1(r=-0.385, P<0.05) in parathyroid cells.ConclusionsThe expression of ERK1/2had no difference between control group and SHPT group, but the expression of p-ERKl/2and Egr-1in SHPT group decreased significantly, and serum PTH and FGF-23was negatively correlated with the expression of ERK1/2, p-ERKl/2, Egr-1in parathyroid cells, which means the disorder of ERK1/2phosphorylation pathway may contribute to the hyperplasia of parathyroid cells and high level of PTH. ERK1/2signal pathway may play an important role in the pathogenesis of SHPT. The conclusion can provide theoretical basis for searching new therapy targets of SHPT.