The murine SP-C promoter directs type II cell-specific expression in transgenic mice

Glasser, Stephan W.; Eszterhas, Susan K.; Detmer, Emily A.; Maxfield, Melissa D.; Korfhagen, Thomas R.

doi:10.1152/ajplung.00250.2004

Cited by 23 publications

(15 citation statements)

References 27 publications

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“…In addition, the inclusion of proximal sequences for the regulation of gene expression within the BAC construct decreases the possibility of nonspecific expression of GFP. Previous studies in transgenic lines with a murine SPC promoter provided a plausible explanation that species differences, including their chromatin environments, may account for the aberrant bronchiolar expression obtained from the human SPC promoter, rather than position effects or the copy number of transgenes (30,32). Finally, a GFP 1 cell in SPC H2B-GFP mice may no longer be expressing SPC, but rather its precursor cell expressed SPC, and GFP is simply observed before protein decay.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies also demonstrated the importance of species-specific promoter use for proper AT2 cell expression (30,31). Further detailed analysis of the murine SPC gene promoter revealed the particular sequences needed for (Received in original form November 22, 2011 and in final form October 19, 2012) AT2 cell-specific expression (32). More recently, the creation of SPC-reverse tetracycline transactivator (rtTA) and SPC-Cre knock-in mice that are useful for analyzing AT2 cells in vivo has also been reported (8,21).…”

mentioning

confidence: 96%

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Surfactant Protein–C Chromatin-Bound Green Fluorescence Protein Reporter Mice Reveal Heterogeneity of Surfactant Protein C–Expressing Lung Cells

Kim

Gludish

Roach

et al. 2013

Am J Respir Cell Mol Biol

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The regeneration of alveolar epithelial cells is a critical aspect of alveolar reorganization after lung injury. Although alveolar Type II (AT2) cells have been described as progenitor cells for alveolar epithelia, more remains to be understood about how their progenitor cell properties are regulated. A nuclear, chromatin-bound green fluorescence protein reporter (H2B-GFP) was driven from the murine surfactant protein-C (SPC) promoter to generate SPC H2B-GFP transgenic mice. The SPC H2B-GFP allele allowed the FACSbased enrichment and gene expression profiling of AT2 cells. Approximately 97% of AT2 cells were GFP-labeled on Postnatal Day 1, and the percentage of GFP-labeled AT2 cells decreased to approximately 63% at Postnatal Week 8. Isolated young adult SPC H2B-GFP 1 cells displayed proliferation, differentiation, and selfrenewal capacity in the presence of lung fibroblasts in a Matrigelbased three-dimensional culture system. Heterogeneity within the GFP 1 population was revealed, because cells with distinct alveolar and bronchiolar gene expression arose in three-dimensional cultures. CD74, a surface marker highly enriched on GFP 1 cells, was identified as a positive selection marker, providing 3-fold enrichment for AT2 cells. In vivo, GFP expression was induced within other epithelial cell types during maturation of the distal lung. The utility of the SPC H2B-GFP murine model for the identification of AT2 cells was greatest in early postnatal lungs and more limited with age, when some discordance between SPC and GFP expression was observed. In adult mice, this allele may allow for the enrichment and future characterization of other SPC-expressing alveolar and bronchiolar cells, including putative stem/progenitor cell populations.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 96%

Surfactant Protein–C Chromatin-Bound Green Fluorescence Protein Reporter Mice Reveal Heterogeneity of Surfactant Protein C–Expressing Lung Cells

Kim

Gludish

Roach

et al. 2013

Am J Respir Cell Mol Biol

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“…(25). The SP-C gene promoter also has been shown to be specific for type II cells (12). Our results demonstrate that different ECM molecules and integrin subunits differentially mediate the effects of mechanical strain on fetal type II lung epithelial cell differentiation.…”

Section: Discussionmentioning

confidence: 59%

Integrins β₁, α₆, and α₃contribute to mechanical strain-induced differentiation of fetal lung type II epithelial cells via distinct mechanisms

Sanchez‐Esteban¹,

Wang²,

Filardo³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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-Mechanical forces regulate lung maturation in the fetus by promoting type II epithelial differentiation. However, the cell surface receptors that transduce these mechanical cues into cellular responses remain largely unknown. When distal lung type II epithelial cells isolated from embryonic day 19 rat fetuses were cultured on flexible plates coated with laminin, fibronectin, vitronectin, collagen, or elastin and exposed to a level of mechanical strain (5%) similar to that observed in utero, transmembrane signaling responses were induced under all conditions, as measured by ERK activation. However, mechanical stress maximally increased expression of the type II cell differentiation marker surfactant protein C when cells were cultured on laminin substrates. Strain-induced alveolar epithelial differentiation was inhibited by interfering with cell binding to laminin using soluble laminin peptides (IKVIV or YIGSR) or blocking antibodies against integrin ␤1, ␣3, or ␣6. Additional studies were carried out with substrates coated directly with different nonactivating anti-integrin antibodies. Blocking integrin ␤ 1 and ␣6 binding sites inhibited both cell adhesion and differentiation, whereas inhibition of ␣ 3 prevented differentiation without altering cell attachment. These data demonstrate that various integrins contribute to mechanical control of type II lung epithelial cell differentiation on laminin substrates. However, they may act via distinct mechanisms, including some that are independent of their cell anchoring role. laminin; surfactant protein C LUNG GROWTH AND DEVELOPMENT during fetal life are critical for extrauterine survival. Premature infants are often born before sufficient lung maturation has occurred with resultant increased morbidity and mortality. Lung maturation, in part, is controlled mechanically. For example, fetal thoracic movements, which generate ϳ5% changes of the distal lung surface area (14, 15), and cell tractional forces exerted on extracellular matrix (ECM) within tissues have been shown to be critical regulators of fetal lung development (28,35,43).A key component of lung development is the differentiation of type II epithelial cells, the major source of pulmonary surfactant that prevents alveolar collapse during expiration. These cells also participate in fluid homeostasis in the alveolar lumen, host defense, and restoration of normal alveolar epithelium after lung injury (38). Past studies have shown that application of levels of mechanical strain that simulate the cell distortion produced by fetal breathing movements induces fetal type II epithelial cell maturation and that the ERK pathway mediates this response (41, 43). However, the mechanisms by which lung cells sense mechanical forces via mechanoreceptors to activate this intracellular differentiation pathway remain largely unknown.Interactions between pulmonary epithelial cells and ECM proteins such as laminin or fibronectin or different collagen subtypes modulate lung development (34). Laminin is a major glycoprotein component ...

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“…The relative positions of the upstream SFTPC mutations at -1167bp, -1647bp, and -2385bp overlap with a conserved region between the mouse and human promoters. Deletion analysis of the SFTPC promoter in transgenic mice and stabletransfected mouse lung epithelial cells demonstrated that this region encodes a transcriptional enhancer that requires a chromatin context for full activity [33,34]. These findings suggest that mutations in SFTPC regulatory elements may decrease expression and account for disease similar to mutations within the SFTPC gene structure that reduce expression or processing.…”

Section: Surfactant Protein C (Sp-c) Abnormalities Are Associated Witmentioning

confidence: 92%

Use of Transgenic Mouse Models to Understand the Origins of Familial Pulmonary Fibrosis

Glasser

Senft²

2011

CPB

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Pulmonary fibrosis is an unremitting degenerative lung disease that has an associated high mortality. The major pathological features include the growth of fibroblasts, emergence of myofibroblasts and their production of extracellular matrix that distorts the peripheral lung tissue and impairs respiratory function. Efforts to pharmacologically reduce inflammation, inhibit fibroblast growth, or matrix synthesis have not been successful in ameliorating disease. Genetic mutations associated with rare hereditary forms of interstitial lung disease (ILD) and idiopathic pulmonary fibrosis (IPF) link definitive causes to this enigmatic group of diseases. The generation of mouse models with similar genetic lesions or deficiencies is providing insight into the mechanisms that lead to fibrosis. Mutations that alter components of pulmonary surfactant or surfactant homeostasis have been associated with specific forms of ILD and/or IPF. This small but growing collection of IPF related surfactant dysfunction mutations implicate respiratory epithelial cell injury as an early event in the molecular pathogenesis and progression of fibrosis. Determining the mechanisms for genetically defined examples of IPF should be informative for investigating the larger segment of IPF where the underlying cause remains obscure.

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The murine SP-C promoter directs type II cell-specific expression in transgenic mice

Abstract: . The murine SP-C promoter directs type II cell-specific expression in transgenic mice.

Cited by 23 publications

References 27 publications

Surfactant Protein–C Chromatin-Bound Green Fluorescence Protein Reporter Mice Reveal Heterogeneity of Surfactant Protein C–Expressing Lung Cells

Surfactant Protein–C Chromatin-Bound Green Fluorescence Protein Reporter Mice Reveal Heterogeneity of Surfactant Protein C–Expressing Lung Cells

Integrins β₁, α₆, and α₃contribute to mechanical strain-induced differentiation of fetal lung type II epithelial cells via distinct mechanisms

Use of Transgenic Mouse Models to Understand the Origins of Familial Pulmonary Fibrosis

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The murine SP-C promoter directs type II cell-specific expression in transgenic mice

Abstract: . The murine SP-C promoter directs type II cell-specific expression in transgenic mice.

Cited by 23 publications

References 27 publications

Surfactant Protein–C Chromatin-Bound Green Fluorescence Protein Reporter Mice Reveal Heterogeneity of Surfactant Protein C–Expressing Lung Cells

Surfactant Protein–C Chromatin-Bound Green Fluorescence Protein Reporter Mice Reveal Heterogeneity of Surfactant Protein C–Expressing Lung Cells

Integrins β1, α6, and α3contribute to mechanical strain-induced differentiation of fetal lung type II epithelial cells via distinct mechanisms

Use of Transgenic Mouse Models to Understand the Origins of Familial Pulmonary Fibrosis

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Integrins β₁, α₆, and α₃contribute to mechanical strain-induced differentiation of fetal lung type II epithelial cells via distinct mechanisms