Abstract:
:Goblet cell metaplasia and mucus hypersecretion are observed in many pulmonary diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. However, the regulation of goblet cell differentiation remains unclear. Here, we identify a regulator of this process in an N-ethyl-N-nitrosourea (ENU) screen for modulators of postnatal lung development; Ryk mutant mice exhibit lung inflammation, goblet cell hyperplasia, and mucus hypersecretion. RYK functions as a WNT coreceptor, and, in the developing lung, we observed high RYK expression in airway epithelial cells and moderate expression in mesenchymal cells as well as in alveolar epithelial cells. From transcriptomic analyses and follow-up studies, we found decreased WNT/β-catenin signaling activity in the mutant lung epithelium. Epithelial-specific Ryk deletion causes goblet cell hyperplasia and mucus hypersecretion but not inflammation, while club cell-specific Ryk deletion in adult stages leads to goblet cell hyperplasia and mucus hypersecretion during regeneration. We also found that the airway epithelium of COPD patients often displays goblet cell metaplastic foci, as well as reduced RYK expression. Altogether, our findings reveal that RYK plays important roles in maintaining the balance between airway epithelial cell populations during development and repair, and that defects in RYK expression or function may contribute to the pathogenesis of human lung diseases.
journal_name
Proc Natl Acad Sci U S Aauthors
Kim HT,Yin W,Nakamichi Y,Panza P,Grohmann B,Buettner C,Guenther S,Ruppert C,Kobayashi Y,Guenther A,Stainier DYRdoi
10.1073/pnas.1911071116subject
Has Abstractpub_date
2019-12-17 00:00:00pages
25697-25706issue
51eissn
0027-8424issn
1091-6490pii
1911071116journal_volume
116pub_type
杂志文章abstract::High levels of inbreeding cause populations to become composed of homozygous, inbred lines. High levels of homozygosity limit the effectiveness of recombination, and therefore, retard the rate of decay of linkage (gametic phase) disequilibrium (LD) among mutations. Inbreeding and recombination interact to shape the ex...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0409804102
更新日期:2005-02-15 00:00:00
abstract::Scientific cinematography using ultrafast optical imaging is a common tool to study motion. In opaque organisms or structures, X-ray radiography captures sequences of 2D projections to visualize morphological dynamics, but for many applications full four-dimensional (4D) spatiotemporal information is highly desirable....
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1308650111
更新日期:2014-03-18 00:00:00
abstract::Protein prenylation with farnesyl or geranylgeranyl moieties is an important posttranslational modification that affects the activity of such diverse proteins as the nuclear lamins, the yeast mating factor mata, and the ras oncogene products. In this article, we show that whole retinal cultures incorporate radioactive...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.19.7673
更新日期:1990-10-01 00:00:00
abstract::The high frequency, recent origin, and geographic distribution of the CCR5-Delta 32 deletion allele together indicate that it has been intensely selected in Europe. Although the allele confers resistance against HIV-1, HIV has not existed in the human population long enough to account for this selective pressure. The ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2435085100
更新日期:2003-12-09 00:00:00
abstract::Our ability to interpret seismic observations including the seismic discontinuities and the density and velocity profiles in the earth's interior is critically dependent on the accuracy of pressure measurements up to 364 GPa at high temperature. Pressure scales based on the reduced shock-wave equations of state alone ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0609013104
更新日期:2007-05-29 00:00:00
abstract::IL-17-producing CD27(-) γδ cells (γδ(27-) cells) are widely viewed as innate immune cells that make critical contributions to host protection and autoimmunity. However, factors that promote them over IFN-γ-producing γδ(27+) cells are poorly elucidated. Moreover, although human IL-17-producing γδ cells are commonly imp...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1204327109
更新日期:2012-10-23 00:00:00
abstract::Arrestins are regulatory molecules for G-protein coupled receptor function. In visual rhodopsin, selective binding of arrestin to the cytoplasmic side of light-activated, phosphorylated rhodopsin (P-Rh*) terminates signaling via the G-protein transducin. While the "phosphate-sensor" of arrestin for the recognition of ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1015461108
更新日期:2011-11-15 00:00:00
abstract::The final step of ethylene biosynthesis in plants is catalyzed by the enzyme 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase (ACCO). In addition to ACC, Fe(II), O2, CO2, and ascorbate are required for in vitro enzyme activity. Direct evidence for the role of the Fe(II) center in the recombinant avocado ACCO has no...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.14.7905
更新日期:1999-07-06 00:00:00
abstract::DNase I hypersensitive regions were mapped within the 17.3-kilobase qa (quinic acid) gene cluster of Neurospora crassa. The 5'-flanking regions of the five qa structural genes and the two qa regulatory genes each contain DNase I hypersensitive sites under noninducing conditions and generally exhibit increases in DNase...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.17.6533
更新日期:1986-09-01 00:00:00
abstract::Regulation of cardiac contraction by neurotransmitters and hormones is often correlated with regulation of the L-type Ca2(+)-channel current (ICa) through the opposite actions of two second messengers, cyclic AMP and cyclic GMP. While cyclic AMP stimulation of ICa is mediated by the activation of cyclic AMP-dependent ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.4.1197
更新日期:1991-02-15 00:00:00
abstract::Knowledge of vibratory patterns in the cochlea is crucial to understanding the stimulation of mechanosensory cells. Experiments to determine the motion of the cochlear partition and surrounding fluid are extremely challenging. As a result, the motion data are incomplete and often contradictory. The bending mechanism o...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0401395101
更新日期:2004-04-20 00:00:00
abstract::Retinoblastoma-related (RBR) genes inhibit the cell cycle primarily by repressing adenovirus E2 promoter binding factor (E2F) transcription factors, which drive the expression of numerous genes required for DNA synthesis and cell cycle progression. The RBR-E2F pathway is conserved in plants, but cereals such as maize ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0813329106
更新日期:2009-03-10 00:00:00
abstract::Ectopic expression of transcription factors can reprogram somatic cells to a pluripotent state. However, most of the studies used skin fibroblasts as the starting population for reprogramming, which usually take weeks for expansion from a single biopsy. We show here that induced pluripotent stem (iPS) cells can be gen...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0908450106
更新日期:2009-09-15 00:00:00
abstract::The BAG6 complex was first identified as an upstream loading factor for tail-anchored membrane proteins entering the TRC40-dependent pathway for posttranslational delivery to the endoplasmic reticulum. Subsequently, BAG6 was shown to enhance the proteasomal degradation of mislocalized proteins by selectively promoting...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1209997109
更新日期:2012-11-20 00:00:00
abstract::Accumulating evidence suggests that α-synuclein (α-syn) occurs physiologically as a helically folded tetramer that resists aggregation. However, the mechanisms underlying the regulation of formation of α-syn tetramers are still mostly unknown. Cellular membrane lipids are thought to play an important role in the regul...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1700465115
更新日期:2018-01-23 00:00:00
abstract::Ceramide, a lipid mediator, has been most closely associated with antiproliferative activities. In this study, we examine the mechanism by which ceramide induces growth suppression and the role of the retinoblastoma gene product (Rb) in this process. Withdrawal of serum from the serum-dependent MOLT-4 cells resulted i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.5.1347
更新日期:1995-02-28 00:00:00
abstract::Interleukin 6 (IL-6) is a cytokine that acts on various cell types. Here we show that IL-6 mRNA is produced in vivo in two self-limiting physiologic angiogenic processes: (i) the formation of the vascular system accompanying development of ovarian follicles and (ii) the formation of a capillary network in the maternal...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.8.3092
更新日期:1990-04-01 00:00:00
abstract::Nasopharyngeal carcinoma (NPC) most frequently occurs in southern China and southeast Asia. Epidemiology studies link NPC to genetic predisposition, Epstein-Barr virus (EBV) infection, and environmental factors. Genetic studies indicate that mutations in chromatin-modifying enzymes are the most frequent genetic altera...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1705236114
更新日期:2017-09-05 00:00:00
abstract::Human pluripotent stem cells have the potential to provide comprehensive model systems for the earliest stages of human ontogenesis. To serve in this capacity, these cells must undergo a targeted, stepwise differentiation process that follows a normal developmental timeline. Here we demonstrate the ability of both hum...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0905245106
更新日期:2009-09-29 00:00:00
abstract::Chemoresistance of cisplatin therapy is related to extensive repair of cisplatin-modified DNA in the nucleus by the nucleotide excision repair (NER). Delivering cisplatin to the mitochondria to attack mitochondrial genome lacking NER machinery can lead to a rationally designed therapy for metastatic, chemoresistant ca...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1405244111
更新日期:2014-07-22 00:00:00
abstract::Bufonid anurans of the genus Atelopus contain both steroidal bufadienolides and various guanidinium alkaloids of the tetrodotoxin class. The former inhibit sodium-potassium ATPases, whereas the latter block voltage-dependent sodium channels. The structure of one guanidinium alkaloid, zetekitoxin AB, has remained a mys...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0400368101
更新日期:2004-03-30 00:00:00
abstract::Accurate calculations of force generated and of ATP flux, in steady isotonic contractions, are made on a simple, two-state muscle model of the sliding filament type. The objective is to illustrate the proper formulation and use of a complete and self-consistent molecular model of muscle. Otherwise, the model is not me...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.71.5.1982
更新日期:1974-05-01 00:00:00
abstract::Chromatophores of Rhodopseudomonas sphaeroides yield the antenna complex B850 in either of two states, depending on the method of isolation. Methods using dodecyl (= lauryl) dimethylamine oxide yield B850 with an absorption spectrum like that in vivo: the bands at 800 and 850 nm, due to the bacteriochlorophyll (Bchl) ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.78.9.5583
更新日期:1981-09-01 00:00:00
abstract::We study the distributions of citations received by a single publication within several disciplines, spanning broad areas of science. We show that the probability that an article is cited c times has large variations between different disciplines, but all distributions are rescaled on a universal curve when the relati...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0806977105
更新日期:2008-11-11 00:00:00
abstract::Utilization of transcription factors might be a powerful approach to modification of metabolism for a generation of crops having superior characteristics because a single transcription factor frequently regulates coordinated expression of a set of key genes for respective pathways. Here, we apply the plant-specific Do...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0402267101
更新日期:2004-05-18 00:00:00
abstract::Seasonal variations in the properties of rabbit-liver fructose 1,6-bisphosphatase have now been linked to corresponding changes in the levels of proteolytic activity in the liver extracts. Incubation of native fructose 1,6-bisphosphatase with purified liver lysosomes causes a 3-fold increase in catalytic activity at p...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.70.2.303
更新日期:1973-02-01 00:00:00
abstract::Drosophila melanogaster Polo kinase physically interacts with, and is repressed by, the Matrimony (Mtrm) protein during oogenesis. Females heterozygous for a deletion of the mtrm gene display defects in chromosome segregation at meiosis I. However, a complete absence of Mtrm results in both meiotic catastrophe and fem...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1301690110
更新日期:2013-03-26 00:00:00
abstract::The 26S proteasome, a molecular machine responsible for regulated protein degradation, consists of a proteolytic core particle (20S CP) associated with 19S regulatory particles (19S RPs) subdivided into base and lid subcomplexes. The assembly of 19S RP base subcomplex is mediated by multiple dedicated chaperones. Amon...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1116538109
更新日期:2012-04-24 00:00:00
abstract::Drosophila melanogaster is a powerful model organism for dissecting the neurogenetic basis of appetitive and aversive behaviors. However, some methods used to assay food preference require or cause starvation. This can be problematic for fly ethanol research because it can be difficult to dissociate caloric preference...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1716880115
更新日期:2018-09-04 00:00:00
abstract::In the primary visual cortex, neurons with similar response preferences are grouped into domains forming continuous maps of stimulus orientation and direction of movement. These properties are widely believed to result from the combination of ascending and lateral interactions in the visual system. We have tested this...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.242399199
更新日期:2002-12-24 00:00:00