Retinoic acid promotes primary fetal alveolar epithelial type II cell proliferation and differentiation to alveolar epithelial type I cells

Abstract

Retinoic acid (RA) plays an important role in lung development and maturation. Many stimuli can induce alveolar epithelial cell damage which will result in the injury of lung parenchyma. The aim of this study was to observe the effect of RA on the proliferation and differentiation of primary fetal alveolar epithelial type II cells (fAECIIs). Primary fAECIIs were isolated from fetal rats at 19 d of gestation and purified by a differential centrifugation and adhesion method. The cells were randomly divided into control (dimethyl sulfoxide, DMSO) and RA groups. Cell proliferation, viability, apoptosis, cycle, and expression of target protein were examined at 24, 48, and 72 h. We found that the proliferation and viability of cells in the RA-exposed group significantly increased compared with the DMSO control group. The proportion (%) of cells in the G2 and S phases in the RA group was significantly higher than that in control group cells. The proportion (%) of both early apoptotic cells and late apoptotic cells decreased significantly in cells exposed to RA compared with cells exposed to DMSO. RA significantly enhanced the expression of aquaporin 5 (AQP5). The expression level of pulmonary surfactant C (SPC) was elevated after cells were exposed to RA for 24 and 72 h but was inhibited when cells were exposed to RA for 48 h. These results suggest that RA promotes fAECII proliferation by improving cell viability, promoting S phase entry and inhibiting apoptosis and RA promotes fAECIIs differentiation to alveolar epithelial type I cells (AECIs).

A role for the liver in parturition and preterm birth

“…The factors thought to modulate AQP expression in placental and fetal membranes include some members of the nuclear receptor superfamily, e.g., the retinoic acid receptors (RARα, β, γ). RA is reported to regulate APQ1, 3, 5 and 9 in other cellular and tissue environments, 45 and the RAR signaling pathway regulates certain target genes in human amniotic membranes, 46 but its role in the fetal membranes has remained uncertain. To answer the question of whether RA regulates APQs in the fetal membranes, Sapin and colleagues cultured explants and primary and established amniotic cells to determine which AQPs were transcriptionally modified by all-trans-RA (the most abundant natural form of retinoic acid).…”

All-trans-retinoic acid regulates aquaporin-3 expression and related cellular membrane permeability in the human amniotic environment

“…We demonstrated that the AQP3 coding gene was regulated by all-trans-retinoic acid in human amnion and epithelial amniotic cells, and previous findings identified this glycoprotein water channel family as retinoic acid-induced in other tissues: atRA stimulation was found to lead to a transactivation of the AQP1 coding gene in human erythroleukemia (HEL) cells [24], to an accumulation of AQP3 mRNA in human keratinocytes [25,26], to an up-regulation of AQP9 in the myeloid leukemia HL-60 cell line [10] and to a stimulation of AQP5 expression in lung epithelial cells [11]. Although AQP1 and 9 are expressed in human fetal membranes, we did not find any atRA increase of either AQP, illustrating the tissue and cellular specificity of transcriptional regulation by this pleiotropic morphogen.…”

SENP1 has an important role in lung development and influences the differentiation of alveolar type 2 cells

“…HUM-iCELL-a002; purchased from iCell Bioscience, Inc., Shanghai, China) were cultured in Dulbeccoֺ’s modified Eagleֺ’s medium/F12 (DME/F-12; HyClone; GE Healthcare Life Sciences, Logan, UT, USA), supplemented with 10% fetal bovine serum (Wisent, Inc., St. Bruno, QC, Canada), in a 5% CO 2 at 37°C. For AT2 differentiation, retinoic acid (RA) was added to medium at 1 µ M ( 23 ). RA powder was purchased from Target Molecule Corp. (Boston, MA, USA) and dissolved in dimethyl sulfoxide.…”