Pin 1/Wnt/β-catenin Signaling Pathway In Mineral Metabolism Disorder Of Chronic Kidney Disease At Gene Level

Objective: Chronic Kidney Disease(CKD) has become one of the major diseases threatening human’s life.Chronic kidney disease–mineral and bone disorder(CKD–MBD) is a systemic disturbance of mineral metabolism that comprises three elements: laboratory abnormalities, bone metabolic abnormalities, and soft tissue mineralization including vascular calcification.CKD-MBD seriously affect the prognosis of disease and quality of life, there are no effective measures to prevention or improvment. Vitamin D has a variety of physiological functions and participates in a variety of disease.The attention of Vitamin D metabolism is increasing in chronic kidney disease patients, and interacts with the Wnt/β-catenin signaling pathways.Emerging evidences suggest that features of CKD-MBD may occur early in disease progression and are associated with changes in osteocyte function. Bone is a new endocrine organ at the heart of CKD-MBD. Changes in osteocyte-specific Wnt/β-catenin signaling may be a common early event in the pathogenesis in bone disorder with CKD-MBD. Dysfunction of Pin1 may occur in the setting of CKD, altering the function of the wnt/β-catenin signaling pathway in CKD-MBD.So we analysis the Vitamin D statues in CKD patients,to identify clinical factors which influence its metabolic disorders; furthermore, by detecting the change of Pin1, β-catenin, Wnt1, SOST, DKK1 and FGF23 m RNA in CKD patients,to understand the clinical significance and risk factors of Pin1/Wnt/β-catenin signaling pathway abnormalities in CKD.Methods: Fouty one patients at CKD stages 1-5D and fourteen Healthy controls that from our hospital were included in this study. In this cross-sectional study,we detected the plasma 25(OH)D by enzyme-linked immunosorbent assay(ELSIA).The m RNA level of Pin1, β-catenin, Wnt1, SOST, DKK1 and FGF23 were detected by RT-PCR. SPSS 20.0 was used for statistical analysis. Results: 25(OH)D levels in different CKD stage is statistical significant(P<0.05), and negatively correlated with the progress of renal function. Diabetes mellitus, the levels of parathyroid hormone(PTH) and e GFR is statistical significant in sufficient and insufficient vitamin D group(P<0.05). 25(OH) D levels were positively correlated with loge GFR.On the contrary, 25(OH) D levels were negatively correlated with log PTH and age. A multivariate linear regression analysis indicated that 25(OH) D levels were independently associated with age and PTH.The Pin1, β-catenin, SOST and FGF23 m RNA levels in CKD patients comparison withhealthy controls showed significant difference(P<0.05), and CKD patients have lowly expression. In addition, the expression of SOST rising gradually along with the deterioration of renal functions. Pin1 and β-catenin, as well as Wnt1, were positively correlated. SOST and e GFR were positively correlated, FGF23 and PTH were inversely. The ROC curve analysis shows that SOST and FGF23 alone or combination has no significant statistical significance. Patients with higher e GFR are given priority to low FGF23 and low SOST(almost 75% of CKD1 and 2); more than 80% of CKD5 patients are represent high FGF23 high SOST, low FGF23 high SOST or low FGF23 low SOST. High serum PTH and low 25(OH) D are statistically difference in low FGF23 and low SOST group.Conclusion: Vitamin D deficiency appears early, along with the progress of renal function.25(OH) D deficiency group is often characterized by high PTH levels and low e GFR, and a high incidence in patients with diabetes. HBG, PTH, age and e GFR were the influencing factors of 25(OH) D. And after the correction of the e GFR, age and PTH are main factors influencing the metabolism of the vitamin D. Pin1, β-catenin, SOST and FGF23 Expression is low in CKD patients.Pin1 may involved in the process of CKD-MBD by regulating β-catenin. SOST are negatively correlated with e GFR, and FGF23 were positively correlated with PTH. SOST and FGF23 closely associated with bone mineral metabolism disorder for CKD patients, but the area under the ROC curve analysis of the two separate or combination have no significant statistical significance. Patients with lower FGF23 and SOST levels have well minerals and vitamin D metabolism, they present as high e GFR, low PTH and high 25(OH) D levels.