Interstitial Fibroblast Proliferation Research Articles

Fibroblasts of rabbit kidney in culture. II. Paracrine stimulation of papillary fibroblasts by PDGF.

To examine the role of tubulointerstitial cell interaction in the regulation of fibroblast growth, fibroblasts from the rabbit renal cortex (CF) and papilla (PF) were cocultured with epithelial cells from the same tissue location. Inner medullary collecting duct epithelial cells (IMCDE) or IMCDE-conditioned medium stimulated DNA synthesis in PF, whereas proximal tubule epithelium (PTE) had no effect on the proliferation of CF. PF and CF showed a similar mitogenic response to exogenous epidermal growth factor and insulin-like growth factor 1 (IGF-I). Transforming growth factor-beta 1 inhibited growth of both cell types, and basic fibroblast growth factor (bFGF) had no effect on proliferation of either cell type. In contrast, platelet-derived growth factor (PDGF) was a potent mitogen for PF but was only weakly mitogenic for CF. Both CF and PF expressed a similar number of a single-affinity class of PDGF receptors (Kd, 2-4 x 10(-10) M). Assay for growth factor activity in conditioned medium from IMCDE and PTE showed that only IMCDE produced detectable PDGF. IMCDE-stimulated proliferation of PF was partially blocked by an antibody to PDGF, whereas antibodies to IGF-I had no neutralizing effect. The data suggest a role for PDGF in the regulation of interstitial fibroblast proliferation by IMCDE in the renal papilla. This paracrine system may be important in the pathogenesis of some forms of interstitial fibrosis of the kidney.

Experimental pulmonary fibrosis induced by paraquat plus oxygen in rats: A morphologic and biochemical sequential study

Changes in lung structure and collagen metabolism were studied at 1, 2, 3, 4, 6, and 8 weeks in a model of pulmonary fibrosis induced in rats with paraquat plus hyperoxia. Morphologic examination of the lungs revealed that the earliest lesions consisted of severe and irreversible endothelial and alveolar epithelial cell damage. Afterward, an inflammatory process took place, initially dominated by polymorphonuclear leukocytes and then by mononuclear cells, but with the constant presence of granulocytes. From the fourth week on there were fibroblast proliferation and a moderate increase of mast cells. In the early stages alveolitis was focal, but from the second week the lungs were diffusely affected with severe distortion of the architecture. Collagen content was moderately increased in the first 2 weeks and then showed a progressive increment until the end of the experiment. Collagen synthesis was significantly elevated from the fourth week, coinciding with interstitial fibroblast proliferation, although there were some animals that showed increased collagen production from the first week. Collagenolytic activity occurred in 3 stages: at 2 weeks there was increased collagen degradation, at 3, 4, and 6 weeks the values showed a trimodal behavior, and at 8 weeks almost all experimental rats presented an important decrease of collagenolysis. Thus, the development of lung fibrosis was associated first with increased rates of collagen synthesis and later with a decrease of collagen degradation.

Understanding bronchopulmonary dysplasia.

The term bronchopulmonary dysplasia (BPD) was initially introduced to describe chronic pulmonary changes that occurred in certain premature infants following respiratory distress syndrome (RDS). 1 Subsequently, BPD has been recognized as a sequela of other forms of severe lung disease in newborn infants. Bronchopulmonary dysplasia currently is responsible for the prolonged hospitalization of 10% to 20% of neonates who survive with the aid of mechanical ventilatory support. 2,3 Lung pathology in this condition consists of multiple emphysematous areas alternating with atelectasis, bronchiolar mucosal hyperplasia and metaplasia, peribronchial smooth-muscle hypertrophy, and interstitial fibroblast proliferation. 1 Clinically, BPD is characterized by chronic respiratory failure and persistent pulmonary roentgenographic abnormalities. The latter may vary from faint, diffuse opacification to cystic emphysematous changes with air trapping, while functional impairment varies from mild carbon dioxide retention to the need for months of mechanical ventilatory support and Proposed Pathogenesis Factors Involved Susceptible Host Acute Lung Injury

Experimental pulmonary fibrosis induced by trisodium citrate and acid-citrate-dextrose

A single intrapulmonary injection of 3.8% trisodium citrate and acid-citrate-dextrose (ACD) into rabbits results in extensive degeneration and necrosis of alveolar pneumocytes, including the type II pneumocyte, and of bronchiolar or bronchial epithelial cells. Subsequently, the alveoli and alveolar ducts collapse, and the septa and ductal walls adhere to each other, accompanied by the proliferation of interstitial fibroblasts. These fibroblasts produce fibrous connective tissue which is followed by pulmonary fibrosis in 1 week. Epithelial regeneration, especially that resulting from the proliferation of immature type II pneumocytes, occurs around the periphery of the fibrous lesions. The synthesis and release of large amounts of surfactant materials by the proliferated type II pneumocytes may induce the surfactant materials to reopen the air spaces of the collapsed and adhesive alveoli. By 4 weeks those fibrous areas in the pathological lungs become smaller and/or appear normal. These results suggest that this is a useful experimental animal model for pulmonary fibrosis, and that epithelial cells, especially type II pneumocytes, are associated with both the induction of and the recovery from the disorder; in the early stage, interference by reepithelization resulting from type II pneumocyte proliferation may elicit the proliferation of fibroblasts, and in later stages, reepithelization and surfactant synthesis by newly proliferated type II pneumocytes may permit the reopening of collapsed and adhesive air spaces.