Clinical significance of serum and tissue klotho levels in human pancreatic cancer / 中华胰腺病杂志

Objective To investigate the correlation of clinicopathological parameters and prognosis with serum and pancreatic cancer tissue klotho. Methods Immunohistochemistry EnVision two step method was used to assess klotho protein expression of a tissue microarray ( TMA) of 79 pairs of pancreatic tissue and normal surrounding tissue. The serum klotho levels in 39 pancreatic cancer patients and 39 healthy controls who had matched clinical data were measured by ELISA. The relationships between the expression of klotho and the clinicopathological features and survival were analyzed. Results Klotho expression positivity in pancreatic cancer tissue was significantly higher than that in adjacent normal tissues (59. 5％ vs 96. 3％);serum level of klotho was markedly higher in pancreatic cancer patients than that in control group [(670. 30 ± 82. 24)pg/ml vs (310.35 ± 34.65) pg/ml], and both the difference was statistically significant (P<0.001). Klotho expression was negatively associated with tumor clinical stage and lymph node metastasis (P<0. 05), and the expression of klotho did not correlate with patients' gender, age, tumor size, location, local invasion depth and the like. The median survival time in pancreatic cancer patients with positive klotho expression were longer than that in in pancreatic cancer patients with negative klotho expression [(48. 31 ± 6. 94) months vs (19. 50 ±6. 78)months], and the difference was statistically significant (P<0. 01). ROC analysis on serum klotho gave a cutoff value of 376. 51 pg/ml to diagnosis pancreatic cancer with a sensitivity of 84. 6％ and specificity of 87. 2％. Conclusions Klotho level in serum and tissue of pancreatic cancer patients was closely correlated with clinicopathological parameters and prognosis, which may be a potential biomarker for pancreatic cancer.

Relationship between Klotho gene and growth axis GH-IGF1 / 国际儿科学杂志

Klotho was first discovered as an aging-suppressor gene. Klotho protein is highly expressed in the brain and the kidney,but can also serve as a circulating hormone. Evidences suggest that Klotho is involved in calcium phosphate homeostasis,energy metabolism,protection of the cardiovascular system,protection of kid-ney and anti-aging through membrane receptors and hormone-like effects. Currently available studies support a tight interaction between Klotho and the GH-IGF1 axis,with a complex reciprocal regulation between them. On one hand,increased activity of the GH-IGF1 axis upregulates serum Klotho levels,which in turn inhibits the pe-ripheral activity of IGF1,thus forming a negative feedback loop. On the other hand,klotho abrogates the inhibito-ry effect of IGF1 in the pituitary,leading to enhanced GH secretion and further increase of IGF1 production,thus forming a positive feedback loop. In addition,Klotho plays an important role in calcium- phosphate metabolism together with GH-IGF1 and FGF23. In this paper,the regulation of Klotho expression and its relationship with GH-IGF1 axis and mineral metabolism are reviewed briefly.

Association of KL gene G-395A polymorphisms with coronary heart disease and serum cystatin C level in the elderly Chinese Han population in central China / 重庆医学

Objective To investigate the single nucleotide polymorphism at G-395A site of the Klotho (KL) gene and to analyze its correlation with the coronary heart disease(CHD) and serum Cystatin C(Cys C) level in the elderly Chinese Han population in central China.Methods A case-control study was conducted in 278 elderly Chinese Han population in this department,who were divided into CHD group(138 cases)and control group(140 cases) according to bear angiography coronary or not.G-395A polymorphism of KL gene was determined by TaqMan Gene probe method,and the relationship between G-395A polymorphism and coronary heart disease and serum Cys-C level was analyzed.Results Compared with the control group,the frequency of GG genotype of G-395A in CHD group was significantly higher,and the frequency of AA genotype and AG genotype was not statistically significant.The levels of Cys-C in the GG genotype were higher than those in the AA and AG genotypes both in the control group and coronary heart disease group.Conclusion In the elderly Han population in central China,the risk of suffering coronary heart disease is higher among the GG genotype of the G-395A locus of the KL gene.KL gene G-395A site gene mutation may affect the development of atherosclerosis by affecting blood Cys-C levels.

Effect of platelet-rich plasma on wnt3 gene and klotho gene of adipose-derived stem cells of rabbit / 中华医学美学美容杂志

Objective To investigate the effect of platelet-rich plasma (PRP) on starting of wnt3 gene and klotho gene of adipose-derived stem cells (ADSCs) of rabbit.Methods Epididymal adipose tissue stem cells were obtained from New Zealand white rabbits,and the cells identified by morphology and inducing differentiation,and the cells were cultured to the fourth generation,PRP and PPP (platelet-poor plasma) were prepared by traditional centrifugal method from abdominal aortic of rabbit; ADSCs were cultured in culture medium containing PRP (experimental group),PPP (control group) and all medium (blank group) for each 5％ for 24h,48h and 72h.Cells of each group were dissociated and total RNA extracted.Effects of the starting of wnt3 gene and klotho gene were detected by RT-PCR.Results Primary ADSCs of rabbit grew in the way of long spindle swirly.The results of oil red O and alizarin red staining of the ADSCs were positive.Expression of wnt3 gene and klotho gene in the experimental group significantly increased from the results of RT-PCR (P＜0.05).Conclusions PRP can promote proliferation of the ADSCs of rabbit and increase the expression of wnt3 gene and klotho gene significantly.

Growth Hormone-Releaser Diet Attenuates Cognitive Dysfunction in Klotho Mutant Mice via Insulin-Like Growth Factor-1 Receptor Activation in a Genetic Aging Model

BACKGROUND: It has been recognized that a defect in klotho gene expression accelerates the degeneration of multiple age-sensitive traits. Accumulating evidence indicates that aging is associated with declines in cognitive function and the activity of growth hormone (GH)/insulin-like growth factor-1 (IGF-1). METHODS: In this study, we examined whether a GH-releaser diet could be effective in protecting against cognitive impairment in klotho mutant mice. RESULTS: The GH-releaser diet significantly induced the expression of IGF-1 and IGF-1 receptors in the hippocampus of klotho mutant mice. Klotho mutant mice showed significant memory impairments as compared with wild-type mice. In addition, the klotho mutation significantly decreased the expression of cell survival/antiapoptotic factors, including phospho-Akt (p-Akt)/phospho-glycogen synthase kinase3beta (p-GSK3beta), phospho-extracellular signal-related kinase (p-ERK), and Bcl-2, but significantly increased those of cell death/proapoptotic factors, such as phospho-c-jun N-terminal kinase (p-JNK), Bax, and cleaved caspase-3 in the hippocampus. Treatment with GH-releaser diet significantly attenuated both decreases in the expression of cell survival/antiapoptotic factors and increases in the expression of cell death/proapoptotic factors in the hippocampus of klotho mutant mice. In addition, klotho mutation-induced oxidative stress was significantly attenuated by the GH-releaser diet. Consequently, a GH-releaser diet significantly improved memory function in the klotho mutant mice. GH-releaser diet-mediated actions were significantly reversed by JB-1, an IGF-1 receptor antagonist. CONCLUSION: The results suggest that a GH-releaser diet attenuates oxidative stress, proapoptotic changes and consequent dysfunction in klotho mutant mice by promoting IGF-1 expression and IGF-1 receptor activation.

Effect of valsartan on ultrastructure in the brain tissue and expression of Klotho gene in spontaneously hypertensive rats / 中南大学学报(医学版)

Objective To observe the effect of valsartan on brian ultrastructure, Klotho gene and micro-inflammatory factor [intercellular adhesion molecule-1(ICAM-1) and vascular cell adhesion molecule-l(VCAM-1)] expression in spontaneously hypertensive rat models. Methods Ten male spontaneously hypertensive rats of 22 weeks age were selected and randomly divided into a hypertension group and a valsartan intervention group, while another 5 Wistar-kyoto rats were set as a normal contrast group. The brain ultrastructure of the 2 groups was observed by electron microscope. The expression of micro-inflammatory factor (ICAM-1 and VCAM-1)and Klotho gene was detected with RT-PCR, immunohistochemistry, and Western blot, respectively. Results The cerebral neuron damage of spontaneously hypertensive rats whose ultrastructure showed cell-pyknosis, chromatin margination and typical apoptotic body formation were alleviated after the intervention of valsartan. RT-PCR showed that the gene expression of Klotho increased while ICAM-1 and VCAM-1 decreased after valsartan intervention. Immunohistochemistry and Western blot also showed that the protein expression of Klotho increased, while ICAM-1 and VCAM-1 decreased after valsartan intervention. ConclusionValsartan can improve the brain ultrastructure of spontaneously hypertensive rats by increasing the expression of Klotho.