Cellular proliferation and apoptosis in the parathyroid glands - effects of phosphate in vivo and in vitro
FP4 — Training and Mobility of Researchers
- Duration
- 1997-07-12 → 1998-07-11
- EU contribution
- —
- Participants
- 2
- Scheme
- RGI
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Project objective
Research objectives and content Most patients with chronic renal failure develop secondary hyperparathyroidism, characterized by increases of parathyroid gland size and serum parathyroid hormone levels. Since secondary hyperparathyroidism is frequently associated with serious complications like renal osteodystrophies, atherosclerosis, soft tissue calcification, anemia, myocardiocytic fibrosis, etc., it's essential to prevent it. Furthermore, secondary hyperparathyroidism can be present even after renal transplantation, with frequent development of persistent hyperparathyroidism, characterized by refractoriness to the usual therapies. Hyperphosphatemia is a very common finding in chronic renal failure. We have studied the role of hyperphosphatemia in the impairment of secondary hyperparathyroidism, and have demonstrated direct effects of phosphorus increasing parathyroid hormone synthesis and secretion, and inducing a hyperplastic pattern in the parathyroid gland with an evident increase in the gland volume. Since the mechanisms leading to parathyroid gland hyperplasia are poorly defined, it's extremely relevant to study in depth the molecular and cellular mechanisms of parathyroid cell proliferation and programmed cell death. This project includes: i) the study of the effects of phosphate on molecular markers of parathyroid cell hyperplasia, to provide additional knowledgment about the genesis of this pathology, ii) the investigation of a possible phosphate-induced monoclonal pattern of proliferation, by which refractoriness to therapy can be explained, and iii) the assessment of the role of phosphate and calcitriol on programmed cell death (apoptosis), which could contribute to develop new treatments of hyperparathyroidism in chronic renal failure. Training content (objective, benefit and expected impact) This project is an extension of my Ph.D. project, that will make possible studies which cannot be achieved at the University of La Laguna due to it s limitations. For this project, my previous experience with the phosphate-induced hyperparathyroidism rat model will be useful to carry out the experiments in vivo, and my training with the human parathyroid cell culture protocol developed by Dr. Drueke's group will be essential for the studies in vitro. The accumulative experience in the study of processes such as cell proliferation and programmed cell death will be important contributions upon my return to my present laboratory.
Original text from CORDIS.
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