TTF-1 response element is critical for temporal and spatial regulation and necessary for hormonal regulation of human<i>surfactant protein-A2</i>promoter activity

Liu, Dongyuan; Yi, Ming; Smith, Margaret E.; Mendelson, Carole R.

doi:10.1152/ajplung.00069.2008

Cited by 17 publications

(20 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In studies using transgenic mice and transfected type II cells, we observed that a 300-bp region upstream of the rabbit [76–79] and human [80–86] SP-A genes is critical for lung cell-specific, developmental and cAMP/IL-1β-induced expression (Fig. 3).…”

Section: Fetal Signals Leading To the Initiation Of Parturitionmentioning

confidence: 99%

Fetal-to-maternal signaling in the timing of birth

Mendelson

Montalbano

Gao

2017

The Journal of Steroid Biochemistry and Molecular Biology

Self Cite

View full text Add to dashboard Cite

Preterm birth remains the major cause of neonatal morbidity and mortality throughout the world. This is due, in part, to our incomplete understanding of the mechanisms that underlie the maintenance of pregnancy and the initiation of parturition at term. In this article, we review our current knowledge of the complex, interrelated and concerted mechanisms whereby progesterone maintains myometrial quiescence throughout most of pregnancy, as well as those that mediate the upregulation of the inflammatory response and decline in progesterone receptor function leading to parturition. Herein, we review findings that demonstrate a role of the fetus in the timing of birth. Specifically, we focus on our own studies indicating that maturation of the fetal lung and enhanced secretion of the surfactant components, surfactant protein A (SP-A), and the potent inflammatory glycerophospholipid, platelet-activating factor (PAF) initiate a signaling cascade culminating in parturition. Our studies suggest an essential role of steroid receptor coactivators, SRC-1 and SRC-2, which activate expression of genes encoding SP-A and LPCAT1. LPCAT1 is a key enzyme in the synthesis of PAF, as well as DPPC, a highly surface-active glycerophospholipid component of surfactant. Thus, we describe a novel pathway through which the fetus contributes to the initiation of labor by signaling the mother when its lungs have achieved sufficient maturity for survival in an aerobic environment.

show abstract

Section: Fetal Signals Leading To the Initiation Of Parturitionmentioning

confidence: 99%

Fetal-to-maternal signaling in the timing of birth

Mendelson

Montalbano

Gao

2017

The Journal of Steroid Biochemistry and Molecular Biology

Self Cite

View full text Add to dashboard Cite

show abstract

“…In studies using transgenic mice (19,20) and transfected type II cells (21)(22)(23)(24)(25), we found that as little as approximately 300 bp of SP-A 5Ј-flanking sequence mediates lung cell-specific, developmental, and cAMP-regulated expression. This region contains four response elements that are highly conserved in the SP-A genes of various species (26).…”

mentioning

confidence: 94%

“…In recent studies using transgenic mice carrying fusion genes comprised of various amounts of 5Ј-flanking sequence from the hSP-A2 gene fused to hGH, as reporter, we observed that as little as 175 bp of hSP-A2 5Ј-flanking DNA promoted appropriate developmental and lung cell-specific expression. However, the 175-bp genomic region (which lacks the ERRE) was insufficient to mediate cAMP regulation of SP-A promoter activity (20). Collectively, these findings suggest that ERR␣ is an important mediator of SP-A gene expression and its induction by cAMP.…”

mentioning

confidence: 95%

cAMP Enhances Estrogen-Related Receptor α (ERRα) Transcriptional Activity at the SP-A Promoter by Increasing Its Interaction with Protein Kinase A and Steroid Receptor Coactivator 2 (SRC-2)

Liu

Benlhabib

Mendelson

2009

Molecular Endocrinology

Self Cite

View full text Add to dashboard Cite

Estrogen-related receptor (ERR␣) plays a critical role in basal and cAMP-induced expression of the human surfactant protein-A (SP-A) gene in lung type II cells through direct binding to an ERR response element (ERRE, 5Ј-TGACCTTA-3Ј) within its 5Ј-flanking region. Furthermore, protein kinase A (PKA) up-regulates ERR␣ activation of the hSP-A promoter. In the present study, using cultured human fetal lung type II cells, we observed that cAMP enhanced ERR␣ phosphorylation and nuclear expression levels. cAMP/PKA stimulation of ERR␣ activation of the SP-A promoter was blocked by the PKA inhibitor, H89, whereas the MAPK P38 inhibitor, SB203580, and the MAPK kinase inhibitor, PD98059, had negligible to modest effects. This suggests that cAMP acts selectively through PKA to increase ERR␣ transcriptional activity. Of several coactivators tested, steroid receptor coactivator 2 (SRC-2) had the most pronounced effect to increase ERR␣ transcriptional activity at the SP-A promoter; this was enhanced by cotransfection with PKA catalytic subunit (PKAcat). Interestingly, SRC-2, ERR␣, and PKAcat in type II cell nuclear extracts interacted at the ERRE; this was enhanced by cAMP and inhibited by H89. cAMP increased in vivo binding of PKAcat and SRC-2 to the ERRE genomic region in lung type II cells. In mutagenesis studies, three serines (S87, S114, and S277) were found to be critical for PKA and SRC-2 induction of ERR␣ transcriptional activity. Collectively, these findings indicate that cAMP/PKA signaling enhances ERR␣ phosphorylation and nuclear localization, recruitment to the SP-A promoter, and interaction with PKAcat and SRC-2, resulting in the up-regulation of SP-A gene transcription. (Molecular Endocrinology 23: 772-783, 2009)

show abstract

“…Additionally, the ATP-binding cassette, subfamily A, member 3 (ABCA3), an essential transporter that mediates surfactant lipoprotein trafficking and lamellar body biogenesis (32,33), showed only modest, nonsignificant changes in lungs of SRC-1/-2 double-deficient fetuses (Supplemental Figure 1C). hormonal regulation of expression (18,19). Steroid receptor coactivators 1 and 2, SRC-1 and SRC-2, serve important roles in transcriptional upregulation of SP-A gene expression in fetal lung type II cells (20,21).…”

Section: Introductionmentioning

confidence: 99%