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Effects of All-Trans-Retinoic Acid in Promoting Alveolar Repair*

Paula N. Belloni, PhD; Laura Garvin, BS; Cheng-Ping Mao, MS; Irene Bailey-Healy, BA; David Leaffer, BA
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*From Roche Bioscience, Department of Respiratory Diseases, Palo Alto, CA.

Correspondence to: Paula Belloni, PhD, Roche Bioscience, Respiratory Diseases, 3401 Hillview Ave, Palo Alto, CA 94308



Chest. 2000;117(5_suppl_1):235S-241S. doi:10.1378/chest.117.5_suppl_1.235S
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Abbreviations: ATRA = all-trans-retinoic acid; PCNA = proliferating cell nuclear antigen; PDGF = platelet-derived growth factor; RA = retinoic acid; RAR = retinoic acid receptor; RXR = retinoid X receptor; SP = surfactant protein; TGF = transforming growth factor

Emphysema is characterized by airway destruction distal to the terminal bronchioles, gradual loss of lung recoil, decreased alveolar surface area, and impaired gas exchange, leading to a reduced FEV1.1 These last two features, impaired gas exchange and reduction in expiratory flow, are characteristic physiologic abnormalities in patients with emphysema. The most common cause of emphysema is cigarette smoking, although other potential environmental toxins also may contribute. These various insulting agents activate destructive processes in the lung, including the release of active proteases and free radical oxidants in excess of protective mechanisms. The imbalance in protease/antiprotease levels leads to the destruction of the elastin matrix and alveolar structure with progressive loss of lung recoil. Removing the injurious agents (ie, quitting smoking) slows the rate of damage; however, unlike the response after acute lung injury, the damaged alveolar structures do not repair and lung function is not regained.

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