Glucocorticoid regulation of human pulmonary surfactant protein-B (SP-B) mRNA stability is independent of activated glucocorticoid receptor

Tillis, Ceá C.; Huang, Helen W.; Bi, Weizhen; S, Pan; Bruce, Shirley R.; Alcorn, Joseph L.

doi:10.1152/ajplung.00420.2010

Cited by 17 publications

(25 citation statements)

References 59 publications

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“…Furthermore, non-GR-mediated genomic responses to synthetic GC treatment have been reported recently (15,37,54). In addition, GCs may induce muscle atrophy secondary to their effects on other cell types or tissues; i.e., the effects on skeletal muscle myofibers may not be completely cell autonomous.…”

mentioning

confidence: 99%

A cell-autonomous role for the glucocorticoid receptor in skeletal muscle atrophy induced by systemic glucocorticoid exposure

Watson

Baehr

Reichardt

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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Glucocorticoids (GCs) are important regulators of skeletal muscle mass, and prolonged exposure will induce significant muscle atrophy. To better understand the mechanism of skeletal muscle atrophy induced by elevated GC levels, we examined three different models: exogenous synthetic GC treatment [dexamethasone (DEX)], nutritional deprivation, and denervation. Specifically, we tested the direct contribution of the glucocorticoid receptor (GR) in skeletal muscle atrophy by creating a muscle-specific GR-knockout mouse line (MGR(e3)KO) using Cre-lox technology. In MGR(e3)KO mice, we found that the GR is essential for muscle atrophy in response to high-dose DEX treatment. In addition, DEX regulation of multiple genes, including two important atrophy markers, MuRF1 and MAFbx, is eliminated completely in the MGR(e3)KO mice. In a condition where endogenous GCs are elevated, such as nutritional deprivation, induction of MuRF1 and MAFbx was inhibited, but not completely blocked, in MGR(e3)KO mice. In response to sciatic nerve lesion and hindlimb muscle denervation, muscle atrophy and upregulation of MuRF1 and MAFbx occurred to the same extent in both wild-type and MGR(e3)KO mice, indicating that a functional GR is not required to induce atrophy under these conditions. Therefore, we demonstrate conclusively that the GR is an important mediator of skeletal muscle atrophy and associated gene expression in response to exogenous synthetic GCs in vivo and that the MGR(e3)KO mouse is a useful model for studying the role of the GR and its target genes in multiple skeletal muscle atrophy models.

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mentioning

confidence: 99%

A cell-autonomous role for the glucocorticoid receptor in skeletal muscle atrophy induced by systemic glucocorticoid exposure

Watson

Baehr

Reichardt

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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“…Stability of specific mRNAs was assayed as described previously (31). Cells were transfected with plasmid DNA according to the protocol prescribed by the Lipofectamine Plus reagent (Invitrogen) with slight modifications; 4 g of plasmid combined with 12 l of Lipofectamine reagent and 12 l of the Plus reagent were utilized to transfect 60-mm plates.…”

Section: Methodsmentioning

confidence: 99%

“…Cytosolic proteins derived from human alveolar epithelial cells specifically bind this 126-nt-long segment. DEX-induced stabilization of human SP-B mRNA does not require the activity of the glucocorticoid receptor or ongoing protein synthesis (31,32). Those results suggest that the mechanism responsible for DEX-induced stabilization of SP-B mRNA is mediated by posttranscriptional or nongenomic effects of glucocorticoids on proteins that bind a specific region of the human SP-B mRNA 3=-UTR.…”

mentioning

confidence: 85%

“…We previously described a reproducible, easily assayable plasmid-based method in which steady-state levels of SP-B mRNA reflect changes in mRNA stability (31). Hormonal regulation of human SP-B mRNA stability was characterized in cells transfected with plasmids encoding full-length SP-B cDNA and the green fluorescent protein (GFP) under transcriptional control of separate, identical promoters.…”

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confidence: 99%

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Sequences of a hairpin structure in the 3′-untranslated region mediate regulation of human pulmonary surfactant protein B mRNA stability

Huang

Payne

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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The ability of pulmonary surfactant to reduce alveolar surface tension requires adequate expression of surfactant protein B (SP-B). Dexamethasone (DEX, 10(-7) M) increases human SP-B mRNA stability by a mechanism that requires a 126-nt-long segment (the 7.6S region) of the 3'-untranslated region (3'-UTR). The objective of this study was to identify sequences in the 7.6S region that mediate regulation of SP-B mRNA stability. The 7.6S region was found to be sufficient for DEX-mediated stabilization of mRNA. Sequential substitution mutagenesis of the 7.6S region indicates that a 90-nt region is required for DEX-mediated stabilization and maintenance of intrinsic stability. In this region, one 30-nt-long element (002), predicted to form a stem-loop structure, is sufficient for DEX-mediated stabilization of mRNA and intrinsic mRNA stability. Cytosolic proteins specifically bind element 002, and binding activity is unaffected whether proteins are isolated from cells incubated in the absence or presence of DEX. While loop sequences of element 002 have no role in regulation of SP-B mRNA stability, the proximal stem sequences are required for DEX-mediated stabilization and specific binding of proteins. Mutation of the sequences that comprise the proximal or distal arm of the stem negates the destabilizing activity of element 002 on intrinsic SP-B mRNA stability. These results indicate that cytosolic proteins bind a single hairpin structure that mediates intrinsic and hormonal regulation of SP-B mRNA stability via mechanisms that involve sequences of the stems of the hairpin structure.

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“…Although, the mechanism by which GCs enhance fetal lung maturity is not well established, the administration of antenatal GCs in threatened preterm labour was widely recommended by many institutes. For instance, the National Institutes of Health (NIH) published a Consensus Development Conference Statement in 1994 on the use of antenatal GCs (101) Recently, there are many evidences that GCs induce fetal lung maturity at both transcriptional and post transcriptional levels (104)(105)(106). Pulmonary surfactant is a complex lipoprotein which main action is to reduce surface tension in the alveoli, and subsequently prevent alveolar collapse upon expiration (107).…”

Section: Antenatal Synthetic Steroid (Dexamethasone and Betamethsone)mentioning

confidence: 99%

Glucocorticoids: Biochemical Group That Play Key Role in Fetal Programming of Adult Disease

Erhuma¹

2012

Glucocorticoids - New Recognition of Our Familiar Friend

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Glucocorticoid regulation of human pulmonary surfactant protein-B (SP-B) mRNA stability is independent of activated glucocorticoid receptor

Cited by 17 publications

References 59 publications

A cell-autonomous role for the glucocorticoid receptor in skeletal muscle atrophy induced by systemic glucocorticoid exposure

A cell-autonomous role for the glucocorticoid receptor in skeletal muscle atrophy induced by systemic glucocorticoid exposure

Sequences of a hairpin structure in the 3′-untranslated region mediate regulation of human pulmonary surfactant protein B mRNA stability

Glucocorticoids: Biochemical Group That Play Key Role in Fetal Programming of Adult Disease

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