Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this research was to determine the effects of vitamin A deficiency on liver and lung morphology and type II pneumocyte function. Weanling rats were fed a retinol-adequate (control) or -deficient diet for 6 wk. Average food intakes and body weights were not different between the vitamin A-deficient and -adequate rats. Histologic examination revealed that the lungs of vitamin A-deficient rats had less collagen in the adventitia of small caliber arteries and arterioles and in the alveolar septa, which appeared thinner than that of controls. Many areas of the lungs of the same rats were also emphysematous (increased size of air spaces distal to the terminal bronchiole, with thinning and partial or total destruction of septal wall). Content of elastin also was lower in the lung parenchyma, as well as in the small arteries and arterioles, but not in the larger ones. Peribronchial collagen was not affected by the deficient diet. Scattered inflammation was observed in most of the vitamin A-deficient rats; a mild inflammatory reaction also was seen in one of the controls. Vitamin A-deficient rats also exhibited hepatocyte vacuolization and mild inflammation in the liver, specifically in the periportal tracts. Surfactant synthesis and ornithine decarboxylase activity were significantly lower in type II pneumocytes isolated from vitamin A-deficient rats. In conclusion, our data provide evidence that vitamin A deficiency produces profound morphologic alterations in liver and lung parenchyma and impairs pneumocyte function.
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PMID:Vitamin A deficiency injures lung and liver parenchyma and impairs function of rat type II pneumocytes. 1080 13

Excess of Vitamin A (retinol) and related compounds (retinoids) induces bone fragility and is associated with increased hip fracture incidence in humans. Yet, their impact on the adult skeleton has been studied in relatively little detail. It is assumed that they induce generalized bone loss and decrease long-bone thickness due to reduction of radial bone growth. Here we characterized early skeletal responses of adult rodents to retinoid treatment, revealing novel aspects of retinoid action on the mature skeleton. The retinoid Ro 13-6298, given subcutaneously for 4 days, induced bone loss in the hind limbs of 12- and 56-week-old rats and of 15-week-old mice. In vivo monitoring of bone mass and geometry changes by peripheral quantitative computed tomography demonstrated that bone mass decline was due to subperiosteal cortical bone loss, which induced a shrinkage of bone diameter, whilst cancellous bone mass was preserved. We observed that the native retinoic acid isomer all-trans RA induced an identical pattern of bone loss. Histomorphometric evaluation revealed that increased subperiosteal osteoclastic bone resorption caused the cortical bone destruction. Interestingly, bone resorption was suppressed in cancellous bone, which was in agreement with reduced in vitro formation of osteoclasts from bone marrow cells that were derived from the proximity of cancellous bone. The retinoid-induced increase in subperiosteal bone resorption could be blocked by bisphosphonate as direct potent inhibitor of osteoclast action, but not by estradiol. Retinoid treatment induced a reduction of bone-forming surfaces at the subperiosteal site, but not in cancellous bone. In vitro osteoblast performance was also reduced or unchanged, depending on the cellular system used and assay type/duration. In conclusion, our studies revealed that the impact of retinoids on bone is highly bone-compartment-specific at early treatment phases. Furthermore, we showed that bone diameter shrinks in the adult skeleton after retinoid treatment due to subperiosteal osteoclastic bone resorption. Thus, retinoid-induced bone thinning is not only due to reduced radial bone growth as previously assumed. Our findings might explain why high intake of retinol is associated with increased hip fracture risk in the elderly and suggest a therapy to prevent such potential negative effects.
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PMID:Retinoid-induced bone thinning is caused by subperiosteal osteoclast activity in adult rodents. 1578 Sep 46

Vitamin A signals play critical roles during embryonic development. In particular, heart morphogenesis depends on vitamin A signals mediated by the retinoid X receptor alpha (RXRalpha), as the systemic mutation of this receptor results in thinning of the myocardium and embryonic lethality. However, the molecular and cellular mechanisms controlled by RXRalpha signaling in this process are unclear, because a myocardium-restricted RXRalpha mutation does not perturb heart morphogenesis. Here, we analyze a series of tissue-restricted mutations of the RXRalpha gene in the cardiac neural crest, endothelial, and epicardial lineages, and we show that RXRalpha signaling in the epicardium is required for proper cardiac morphogenesis. Moreover, we detect an additional phenotype of defective coronary arteriogenesis associated with RXRalpha deficiency and identify a retinoid-dependent Wnt signaling pathway that cooperates in epicardial epithelial-to-mesenchymal transformation.
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PMID:Epicardial retinoid X receptor alpha is required for myocardial growth and coronary artery formation. 1635 30