Retinoids bind to nuclear receptors [retinoic acid receptors (RARs) and retinoid X receptors]. RARbeta, one of three isoforms of RARs (alpha, beta, and gamma), is expressed in the fetal and adult lung. We hypothesized that RARbeta plays a role in alveolarization. Using morphometric analysis, we determined that there was a significant increase in the volume density of airspace in the alveolar region of the lung at 28, 42, and 56 d postnatal age in RARbeta null mice when compared with wild-type controls. The mean cord length of the respiratory airspaces was increased in RARbeta null animals at 42 d postnatal age. Respiratory gas-exchange surface area per unit lung volume was significantly decreased in RARbeta null animals at 28, 42, and 56 d postnatal age. In addition, alveolar ducts tended to comprise a greater proportion of the lung airspaces in the RARbeta null mice. The RARbeta null mice also had impaired respiratory function when compared with wild-type control mice. There was no effect of RARbeta gene deletion on lung platelet-derived growth factor (PDGF) receptor alpha mRNA levels in postnatal lung tissue at several postnatal ages. However PDGF-A protein levels were significantly lower in the RARbeta null mice than in wild-type controls. Thus, deletion of the RARbeta gene impairs the formation of the distal airspaces during the postnatal phase of lung maturation in mice via a pathway that may involve PDGF-A.
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http://dx.doi.org/10.1203/01.PDR.0000151315.81106.D3 | DOI Listing |
J Biol Chem
July 2018
From the Departments of Pharmacology and
All--retinoic acid (RA), a potent inducer of cellular differentiation, functions as a ligand for retinoic acid receptors (RARα, β, and γ). RARs are activated by ligand binding, which induces transcription of direct genomic targets. However, whether embryonic stem cells respond to RA through routes that do not involve RARs is unknown.
View Article and Find Full Text PDFMol Neurobiol
July 2017
Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 rue Laurent Fries, 67404, Illkirch Cedex, France.
Retinoic acid (RA) signaling through retinoic acid receptors (RARs), known for its multiple developmental functions, emerged more recently as an important regulator of adult brain physiology. How RAR-mediated regulation is achieved is poorly known, partly due to the paucity of information on critical target genes in the brain. Also, it is not clear how reduced RA signaling may contribute to pathophysiology of diverse neuropsychiatric disorders.
View Article and Find Full Text PDFNucl Recept Signal
June 2015
Goodman Cancer Research Centre, 1160 Pine Avenue West, McGill University, Montréal, Québec H3A 1A3 (XL, VG) and Departments of Biochemistry, Medicine and Oncology, 3655 Promenade Sir William Osler, McGill University, Montréal, Québec H3G 1Y6 (VG), Canada .
Retinoic acid receptor β (RARβ) has been proposed to act as a tumor suppressor in breast cancer. In contrast, recent data have shown that RARβ promotes ERBB2-induced mammary gland tumorigenesis through remodeling of the stromal compartment and activation of cancer-associated fibroblasts. However, it is currently unknown whether RARβ oncogenic activity is specific to ERBB2-induced tumors, or whether it influences the initiation and progression of other breast cancer subtypes.
View Article and Find Full Text PDFPLoS One
August 2014
Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China.
Introduction: Accurate prediction of the biochemical recurrence (BCR) is critical for patients after intended curative therapy like radical prostatectomy (RP) or definitive radiotherapy for prostate cancer. Glutathione-S-transferases polymorphisms as well as hypermethylation of GSTP1 and functional genes in carcinogenesis, including tumor suppression gene (APC), hormone receptor that regulates cell growth and differentiation gene (RARbeta) were reported to be associated with BCR. Nevertheless, the reported results are inconsistent.
View Article and Find Full Text PDFArch Med Sci
April 2013
Nutritional Research Center and Key Laboratory of Developmental Diseases in Childhood, Ministry of Education, Children's Hospital, Chongqing Medical University, Chongqing, China.
Introduction: The retinoic acid (RA) signaling pathway plays important roles in neural development. All-trans retinoic acid (ATRA) activates the RA signal by regulating RAR-β in mesenchymal stem cell (MSC)-derived neuron cells. Here, we try to investigate whether RAR-β over-expression can affect neuronal differentiation of MSCs.
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