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Retinoic Acid Signaling and Development of the Respiratory System

  • Hector A. Marquez
  • Felicia ChenEmail author
Chapter
  • 92 Downloads
Part of the Subcellular Biochemistry book series (SCBI, volume 95)

Abstract

Retinoic acid (RA), the bioactive metabolite of vitamin A (VA), has long been recognized as a critical regulator of the development of the respiratory system. During embryogenesis, RA signaling is involved in the development of the trachea, airways, lung, and diaphragm. During postnatal life, RA continues to impact respiratory health. Disruption of RA activity during embryonic development produces dramatic phenotypes in animal models and human diseases, including tracheoesophageal fistula, tracheomalacia, congenital diaphragmatic hernia (CDH), and lung agenesis or hypoplasia. Several experimental methods have been used to target RA pathways during the formation of the embryonic lung. These have been performed in different animal models using gain- and loss-of-function strategies and dietary, pharmacologic, and genetic approaches that deplete retinoid stores or disrupt retinoid signaling. Experiments utilizing these methods have led to a deeper understanding of RA’s role as an important signaling molecule that influences all stages of lung development. Current research is uncovering RA cross talk interactions with other embryonic signaling factors, such as fibroblast growth factors, WNT, and transforming growth factor-beta.

Keywords

Retinoic acid Vitamin A Retinoid Signaling Vitamin A deficiency Respiratory Lung Development Embryonic Growth Vertebrates Mammal Avian Retinoic acid regulated pathways 

Abbreviations

ACTA2

Alpha-actin-2 or alpha smooth muscle actin

ALDH

Aldehyde dehydrogenase

ASM

Airway smooth muscle

BMP4

Bone morphogenetic protein 4

BMS493

A pan-retinoic acid receptor inverse agonist

CDH

Congenital diaphragmatic hernia

COPD

Chronic obstructive pulmonary disease

DEAB

Diethylaminobenzaldehyde

DKK1

Dickkopf WNT signaling pathway inhibitor 1

E

Embryonic day

FGF

Fibroblast growth factor

GLI

GLI-Kruppel family member

HH

Hedgehog

MYH11

Myosin heavy chain 11

MYOCD

Myocardin

n.d.

Not determined

NKX2.1

NK2 homeobox 1

p.c.

Post coitum

PH

Pulmonary hypertension

PN

Postnatal day

RA

Retinoic acid

RAD

Retinoic acid deficiency or retinoic acid-deficient

RALDH

Retinaldehyde dehydrogenase

RAR

Retinoic acid receptor

RARE

Retinoic acid response element

SHH

Sonic hedgehog

SRF

Serum response factor

STRA6

Stimulated by retinoic acid 6

TAGLN

Transgelin

TEF

Tracheoesophageal fistula

TGFβ

Transforming growth factor-beta

VA

Vitamin A

VAD

Vitamin A deficiency or vitamin A-deficient

WNT

Wingless-type MMTV integration site family

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Authors and Affiliations

  1. 1.Pulmonary CenterBoston University School of MedicineBostonUSA

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