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Retinoic acid treatment abrogates elastase-induced pulmonary emphysema in rats

An Erratum to this article was published on 01 July 1997

Abstract

Pulmonary emphysema is a common disease1 in which destruction of the lung's gas-exchange structures (alveoli)2 leads to inadequate oxygenation3, disability4 and frequently death1; lung transplantation provides its only remediation. Because treatment of normal rats with all-trans-retinoic acid increases the number of alveoli5, we tested whether a similar effect would occur in rats with emphysema. Elastase was instilled into rat lungs, producing changes characteristic of human2 and experimental6 emphysema: increased lung volume reflecting a loss of lung elastic recoil, larger but fewer alveoli and diminished volume-corrected alveolar surface area due to destruction of alveolar walls. Treatment with all-trans-retinoic acid reversed these changes providing nonsurgical remediation of emphysema and suggesting the possibility of a similar effect in humans.

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References

  1. Guyer, B., Strobino, D.M., Ventura, S.J., MacDorman, M. & Martin, J.A. Annual summary of vital statistics — 1995. Pediatrics 98, 1007–1019 (1996).

    CAS  PubMed  Google Scholar 

  2. Thurlbeck, W.H. Internal surface area and other measurements in emphysema. Thorax 22, 483–496 (1967).

    Article  CAS  Google Scholar 

  3. West, J.R., Baldwin, E.de F., Cournand, A. & Richards, D.W., Jr. Physiopathologic aspects of chronic pulmonary emphysema. Am.J. Med 10, 481–496 (1951).

    Article  CAS  Google Scholar 

  4. Murray, C.J.L. & Lopez, A.D. Evidence-based health policy – lessons from the global burden of disease study. Science 274, 740–743 (1996).

    Article  CAS  Google Scholar 

  5. Massaro, G.D. & Massaro, D. Postnatal treatment with retinoic acid increases the number of pulmonary alveoli in rats. Am.J.Physiol. 270, L305–L310 (1996).

    CAS  PubMed  Google Scholar 

  6. Kaplan, P.D., Kuhn, C. & Pierce, J.A. The induction of emphysema with elastase. 1. The evolution of the lesion and the influence of serum. J. Lab. din. Med. 82, 349–356 (1973).

    CAS  Google Scholar 

  7. Massaro, G.D. & Massaro, D. Formation of pulmonary alveoli and gas-exchange surface area: Quantitation and regulation. Annu. Rev. Physiol. 58, 73–92 (1996).

    Article  CAS  Google Scholar 

  8. Okabe, T., Yorifuji, H., Yamada, E. & Takaku, F. Isolation and characterization of vitamin-A-storing lung cells. Exp. Cell. Res. 154, 125–135 (1984).

    Article  CAS  Google Scholar 

  9. Massaro, D. & Massaro, G.D. Dexamethasone accelerates alveolar wall thinning and alters wall composition. Am. J. Physiol. 251, R218–R224 (1986).

    CAS  PubMed  Google Scholar 

  10. Ong, D.E. & Chytil, F. Changes in levels of cellular retinol- and retinoic-acid-binding protein of liver and lung during perinatal development of rat. Proc. Natl. Acad. Sci. USA 73, 3976–3978 (1976).

    Article  CAS  Google Scholar 

  11. Grummer, M.A. & Zachman, R.D. Postnatal rat lung retinoic acid receptor (RAR) mRNA expression and effects of dexamethasone on RAR-βmRNA. Pediatr. Pulmonol. 20, 234–240 (1995).

    Article  CAS  Google Scholar 

  12. Massaro, D., Teich, N., Maxwell, S., Massaro, G.D. & Whitney, P. Postnatal development of alveoli: Regulation and evidence for a critical period in rats. J. Clin. Invest. 76, 1297–1305 (1985).

    Article  CAS  Google Scholar 

  13. Rush, M.G., Riaz-Ul-Hag & Chytil, F. Opposing effects of retinoic acid and dexamethasone on cellular retinol-binding protein ribonucleic acid levels in the rat. Endocrinology 129, 705–709 (1991).

    Article  CAS  Google Scholar 

  14. Karlinsky, J.B. & Snider, G.L. Animal models of emphysema. Am. Rev. Respir. Dis. 117, 1109–1133 (1978).

    CAS  PubMed  Google Scholar 

  15. Tenny, S.M. & Remmers, J.E. Comparative quantitative morphology of the mammalian lung: Diffusing area. Nature 197, 54–56 (1963).

    Article  Google Scholar 

  16. Christie, R.V. The elastic properties of the emphysematous lung and their significance. J. Clin. Invest 13, 295–321 (1934).

    Article  CAS  Google Scholar 

  17. Gilchrest, B.A. Turning back the clock: Retinoic acid modifies intrinsic aging changes. J. Clin. Invest. 94, 1711 (1994).

    Article  CAS  Google Scholar 

  18. Margraf, L.R., Tomashefski, J.F., Jr., Bruce, M.C. & Dahms, B.B. Morphometric analysis of the lung in bronchopulmonary dysplasia. Am. Rev. Respir. Dis. 143, 391–400 (1991).

    Article  CAS  Google Scholar 

  19. Shott, S. Statistics for Health Professionals. 229–268 (Saunders,Philadelphia,Pennsylvania, 1990).

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Massaro, G., Massaro, D. Retinoic acid treatment abrogates elastase-induced pulmonary emphysema in rats. Nat Med 3, 675–677 (1997). https://doi.org/10.1038/nm0697-675

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