170
H. A. Marquez and F. Chen
The Future
Despite major advances in RA biology, there are still many questions about the
molecular and cellular events controlled by vitamin A/RA during the development
of the respiratory system that remain unanswered. There is a need for genetic tools
that allow precise temporal and tissue-specific manipulation of RA activity or RArelated genes. The field also requires a more reliable method to measure RA activity
since circulating VA or RA does not reflect local vitamin A stores or RA activity
in target cells. As technology advances, future studies will provide a more detailed
understanding of when, where, and how RA and its receptors are acting in the developing lung and the rest of the respiratory system. A better understanding of the
developmental events controlled by RA will likely reveal potential therapeutic targets for the prevention and treatment of chronic lung diseases and regeneration of
damaged lungs.
References
Amengual J, Zhang N, Kemerer M, Maeda T, Palczewski K, Von Lintig J (2014) STRA6 is critical
for cellular vitamin A uptake and homeostasis. Hum Mol Genet 23:5402–5417
Anderson DH (1941) Incidence of congenital diphragmatic hernia in the young of rats bred on a
diet deficient in vitamin A. Am J Dis Child 62:888–889
Anderson DH (1949) Effect of diet during pregnancy upon the incidence of congenital diaphragmatic
hernia in the rat. Am J Pathol 25:163–185
Babiuk RP, Thebaud B, Greer JJ (2004) Reductions in the incidence of nitrofen-induced
diaphragmatic hernia by vitamin A and retinoic acid. Am J Physiol Lung Cell Mol Physiol
286:L970-973
Bellusci S, Grindley J, Emoto H, Itoh N, Hogan BL (1997) Fibroblast growth factor 10 (FGF10)
and branching morphogenesis in the embryonic mouse lung. Development 124:4867–4878
Berry DC, Jacobs H, Marwarha G, Gely-Pernot A, O’Byrne SM, DeSantis D, Klopfenstein M, Feret
B, Dennefeld C, Blaner WS, Croniger CM, Mark M, Noy N, Ghyselinck NB (2013) The STRA6
receptor is essential for retinol-binding protein-induced insulin resistance but not for maintaining
vitamin A homeostasis in tissues other than the eye. J Biol Chem 288:24528–24539
Bouillet P, Sapin V, Chazaud C, Messaddeq N, Decimo D, Dolle P, Chambon P (1997) Developmental expression pattern of Stra6, a retinoic acid-responsive gene encoding a new type of membrane
protein. Mech Dev 63:173–186
Burgos CM, Davey MG, Riley JS, Jia H, Flake AW, Peranteau WH (2018) Lung function and
pulmonary artery blood flow following prenatal maternal retinoic acid and imatinib in the nitrofen
model of congenital diaphragmatic hernia. J Pediatr Surg 53:1681–1687
Burri PH (1974) The postnatal growth of the rat lung. 3. Morphology Anat Rec 180:77–98
Carden KA, Boiselle PM, Waltz DA, Ernst A (2005) Tracheomalacia and tracheobronchomalacia
in children and adults: an in-depth review. Chest 127:984–1005
Chazaud C, Dolle P, Rossant J, Mollard R (2003) Retinoic acid signaling regulates murine bronchial
tubule formation. Mech Dev 120:691–700
Checkley W, West KP Jr, Wise RA, Baldwin MR, Wu L, LeClerq SC, Christian P, Katz J, Tielsch JM,
Khatry S, Sommer A (2010) Maternal vitamin A supplementation and lung function in offspring.
N Engl J Med 362:1784–1794
H. A. Marquez and F. Chen
The Future
Despite major advances in RA biology, there are still many questions about the
molecular and cellular events controlled by vitamin A/RA during the development
of the respiratory system that remain unanswered. There is a need for genetic tools
that allow precise temporal and tissue-specific manipulation of RA activity or RArelated genes. The field also requires a more reliable method to measure RA activity
since circulating VA or RA does not reflect local vitamin A stores or RA activity
in target cells. As technology advances, future studies will provide a more detailed
understanding of when, where, and how RA and its receptors are acting in the developing lung and the rest of the respiratory system. A better understanding of the
developmental events controlled by RA will likely reveal potential therapeutic targets for the prevention and treatment of chronic lung diseases and regeneration of
damaged lungs.
References
Amengual J, Zhang N, Kemerer M, Maeda T, Palczewski K, Von Lintig J (2014) STRA6 is critical
for cellular vitamin A uptake and homeostasis. Hum Mol Genet 23:5402–5417
Anderson DH (1941) Incidence of congenital diphragmatic hernia in the young of rats bred on a
diet deficient in vitamin A. Am J Dis Child 62:888–889
Anderson DH (1949) Effect of diet during pregnancy upon the incidence of congenital diaphragmatic
hernia in the rat. Am J Pathol 25:163–185
Babiuk RP, Thebaud B, Greer JJ (2004) Reductions in the incidence of nitrofen-induced
diaphragmatic hernia by vitamin A and retinoic acid. Am J Physiol Lung Cell Mol Physiol
286:L970-973
Bellusci S, Grindley J, Emoto H, Itoh N, Hogan BL (1997) Fibroblast growth factor 10 (FGF10)
and branching morphogenesis in the embryonic mouse lung. Development 124:4867–4878
Berry DC, Jacobs H, Marwarha G, Gely-Pernot A, O’Byrne SM, DeSantis D, Klopfenstein M, Feret
B, Dennefeld C, Blaner WS, Croniger CM, Mark M, Noy N, Ghyselinck NB (2013) The STRA6
receptor is essential for retinol-binding protein-induced insulin resistance but not for maintaining
vitamin A homeostasis in tissues other than the eye. J Biol Chem 288:24528–24539
Bouillet P, Sapin V, Chazaud C, Messaddeq N, Decimo D, Dolle P, Chambon P (1997) Developmental expression pattern of Stra6, a retinoic acid-responsive gene encoding a new type of membrane
protein. Mech Dev 63:173–186
Burgos CM, Davey MG, Riley JS, Jia H, Flake AW, Peranteau WH (2018) Lung function and
pulmonary artery blood flow following prenatal maternal retinoic acid and imatinib in the nitrofen
model of congenital diaphragmatic hernia. J Pediatr Surg 53:1681–1687
Burri PH (1974) The postnatal growth of the rat lung. 3. Morphology Anat Rec 180:77–98
Carden KA, Boiselle PM, Waltz DA, Ernst A (2005) Tracheomalacia and tracheobronchomalacia
in children and adults: an in-depth review. Chest 127:984–1005
Chazaud C, Dolle P, Rossant J, Mollard R (2003) Retinoic acid signaling regulates murine bronchial
tubule formation. Mech Dev 120:691–700
Checkley W, West KP Jr, Wise RA, Baldwin MR, Wu L, LeClerq SC, Christian P, Katz J, Tielsch JM,
Khatry S, Sommer A (2010) Maternal vitamin A supplementation and lung function in offspring.
N Engl J Med 362:1784–1794