Abnormal Collagen Accumulation Research Articles

A ROLE FOR 1,25-DIHYDROXYVITAMIN D3 IN CONTROL OF BONE-MARROW COLLAGEN DEPOSITION?

It is suggested that 1,25-dihydroxyvitamin D3 (1,25-[OH]2D3), the active hormonal metabolite of vitamin D3, inhibits the formation of fibrous tissue (mainly collagen) in bone-marrow and also increases its degradation. 1,25-(OH)2D3 inhibits the proliferation of megakaryocytes which normally promote collagen synthesis. The hormone also directly antagonises collagen synthesis. Degradation of fibrous tissue is mediated by monocytes and macrophages, which contain collagenase, and the number and activity of these cells is increased by 1,25-(OH)2D3. Thus the various actions of this hormone contribute collectively to a reduction in collagen content; conversely a deficiency of 1,25-(OH)2D3 may allow abnormal accumulation of collagen in the marrow.

Elevated Arterial Cyclic AMP Levels during the Onset of Renal Hypertension in Rats

1. To determine the possible role of arterial cyclic AMP in the pathogenesis of hypertensive vascular hypertrophy and hyperplasia, the changes in the level of this nucleotide were studied during the development of renal hypertension in rats with aortic ligation between the renal arteries. 2. A twofold increase in the cyclic AMP level of the thoracic aorta was observed in 9-day hypertensive rats when compared with sham-operated controls. At this time the total amounts of DNA and collagen were unchanged, although a marked increase in arterial fibrous protein was already present. 3. Arterial cyclic AMP remained significantly elevated in the thoracic aorta of 30-day hypertensive animals. At this time the hypertensive vascular alterations had reached completion as shown by the abnormal accumulation of collagen, DNA and non-fibrous protein. 4. Contrary to the events taking place in the thoracic aorta, a marked decrease in cyclic AMP was present in the abdominal portion, which was protected from high blood pressure by the aortic ligature. In this segment decreased cyclic AMP coexisted with an unchanged collagen content and a diminution in the contents of DNA and non-fibrous protein. 5. Thus a marked increase in arterial cyclic AMP precedes the initiation of DNA replication and collagen accumulation in vascular territories subjected to high blood pressure. These studies suggest the participation of this nucleotide in the vascular growth induced by hypertension.

Potentiation of chemically induced lung fibrosis by thorax irradiation

Intraperitoneal injection of butylated hydroxytoluene (BHT) causes epithelial cell death, followed 2–4 days later by extensive proliferation of type II alveolar cells in mouse lung. Five to 8 days after BHT, most dividing cells are capillary endothelial cells or interstitial cells. In animals that were exposed to 200 rad thorax irradiation immediately or 1 day after BHT, lung hydroxyproline was increased 2 weeks later. The response was dose dependent, and the interaction between BHT and thorax irradiation was synergistic. Light microscopy showed abnormal accumulation of collagen in the alveolar septa. Lung hydroxyproline was not increased in animals that were irradiated 6 days after BHT, compared to animals treated with BHT alone. We concluded that fibrosis develops if lung is damaged by a blood-borne agent and radiation to the thorax occurs at a time when it may compromise alveolar reepithelialization. Exposure to X-rays during proliferation of capillary endothelial cells or interstitial cells does not enhance development of fibrosis.