PubMed Health⌕ Search

Biomedical subjects

Wei Yan

Publications and source records attributed to Wei Yan.

At least 19 recordsLinked to original sources
PubMed2026

Glucose-TOR Signaling Regulates Root Hair Elongation in Arabidopsis via the RHD6-RSL4 Transcriptional Cascade.

Root hairs are tubular protrusions of root epidermal cells that expand the root surface area to facilitate water and nutrient uptake. The target of rapamycin (TOR) kinase has been identified as a positive regulator of root hair elongation, and the RHD6-RSL4 bHLH transcriptional cascade is well established as a core module that governs root hair morphogenesis. However, whether TOR signaling acts upstream of the RHD6-RSL4 pathway and how glucose signals are integrated into this transcriptional regulatory network during root hair development remain incompletely understood. In this study, transcriptome profiling combined with pharmacological and genetic functional assays was performed to elucidate the TOR-mediated transcriptional regulatory pathway of root hair elongation in Arabidopsis. Chemical inhibition of TOR triggered genome-wide transcriptional reprogramming in seedling roots, including disruption of auxin and ethylene signal transduction and pronounced downregulation of hundreds of genes related to root hair development. Glucose-activated TOR signaling modulates the expression of root hair-specific (RHS) genes mainly through the core RHD6-RSL4 transcriptional cascade. The transcription of RSL1-RSL5 was strongly dependent on functional TOR activity, whereas RHD6 transcript abundance was specifically induced by glucose-TOR signaling under carbon-starvation recovery conditions. Genetic overexpression of either RHD6 or RSL4 partially rescued root hair elongation defects caused by TOR suppression, confirming that the RHD6-RSL4 cascade functions as a critical downstream transcriptional module of glucose-TOR signaling. Collectively, this work establishes a transcriptional framework in which glucose-TOR signals modulate root hair elongation via transcriptional activation of the master bHLH regulators RHD6 and RSL4.

RHD6-RSL4 cascade↗
PubMed2025

The MYC/TXNIP axis mediates NCL-Suppressed CD8+T cell immune response in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma is a deadly malignancy with immune evasion playing a key role in tumor progression. Glucose metabolism is crucial for T cell function, and the nucleolar protein NCL may influence T cell glucose metabolism. This study aims to investigate NCL's role in T cell glucose metabolism and immune evasion by lung adenocarcinoma cells. METHODS: Utilizing single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), we analyzed cell clustering, annotation, and prognosis. In vitro experiments involved manipulating NCL expression in CD8+ T cells to study immune function and glucose metabolism. In vivo studies using an orthotopic transplant mouse model monitored NCL's impact on CD8+ T cell glucose metabolism and anti-tumor immune function. RESULTS: NCL was associated with T cell dysfunction and glucose metabolism. NCL silencing enhanced CD8+ T cell glucose metabolism, cytotoxicity, and infiltration, while NCL overexpression had the opposite effect. NCL overexpression relieved MYC-mediated transcriptional repression of TXNIP, reducing CD8+ T cell glucose metabolism. In vivo, NCL inhibited CD8+ T cell glucose metabolism through the MYC/TXNIP axis, hindering anti-tumor immune function. CONCLUSIONS: NCL overexpression suppresses CD8+ T cell glucose metabolism and anti-tumor immune function, promoting lung adenocarcinoma progression via the MYC/TXNIP axis.

CD8-Positive T-Lymphocytes↗
PubMed2025

CAFs activated by YAP1 upregulate cancer matrix stiffness to mediate hepatocellular carcinoma progression.

BACKGROUND: The stiffness of the matrix is closely related to the progression of hepatocellular carcinoma (HCC). Although direct targeting of stromal rigidity in HCC remains a clinical challenge, cancer-associated fibroblasts (CAFs) are considered key contributors to this process. Given the heterogeneity of CAFs, this study explored the relationship between specific CAF subsets and liver cancer matrix stiffness, aiming to identify novel therapeutic targets for HCC patients. METHODS: Single-cell sequencing datasets were leveraged to identify cell types within liver cancer and characterize the transcriptomic profiles of CAFs. Prognostic analysis, utilizing the Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) liver cancer datasets, assessed the correlation between matrix stiffness-related genes and HCC patient outcomes. Pseudo-time analysis was applied to trace the developmental trajectories of CAFs. By calculating intercellular communication probabilities and analyzing transcription factor activity, the functions and interactions of different CAF subsets were elucidated. Gene Ontology (GO) analysis was used to explore the functional roles of CAFs in distinct Yes-associated protein 1 (YAP1) groups. Finally, cellular experiments and animal experiments were further conducted to validate the hypotheses of this study. RESULTS: This study identified CAF subpopulations based on single-cell sequencing data and analyzed transcriptional changes within these subpopulations. Key findings include the identification of collagen type I alpha 1 (COL1A1), collagen type III alpha 1 (COL3A1), and lysyloxidase (LOX) as pivotal node genes during CAF development. Moreover, the expression of matrix stiffness-related genes was inversely correlated with the prognosis of HCC patients. Notably, the YAP1-positive CAF subpopulation emerged as the primary contributor to matrix stiffness in liver cancer. This subpopulation upregulates the expression of matrix stiffness-related genes and promotes tumor progression by activating signaling pathways such as autophagy and GTPase activity regulation. Cellular experiments and animal studies further validated this conclusion. CONCLUSION: This single-cell analysis uncovered the functional roles of CAFs in liver cancer. The YAP1-positive CAF subpopulation, in particular, was shown to contribute to matrix stiffness by upregulating the expression of relevant genes and promoting tumor progression through the activation of specific signaling pathways.

Carcinoma, Hepatocellular↗
PubMed2003

HILS1 is a spermatid-specific linker histone H1-like protein implicated in chromatin remodeling during mammalian spermiogenesis.

Chromatin remodeling is a major event that occurs during mammalian spermiogenesis, the process of spermatid maturation into spermatozoa. Nuclear condensation during spermiogenesis is accomplished by replacing somatic histones (linker histone H1 and core histones) and the testis-specific linker histone, H1t, with transition proteins and protamines. It has long been thought that H1t is the only testis-specific linker histone, and that all linker histones are replaced by transition proteins, and subsequently by protamines during spermiogenesis. Here, we report the identification and characterization of a spermatid-specific linker histone H1-like protein (termed HILS1) in the mouse and human. Both mouse and human HILS1 genes are located in intron 8 of the alpha-sarcoglycan genes. HILS1 is highly expressed in nuclei of elongating and elongated spermatids (steps 9-15). HILS1 displays several biochemical properties that are similar to those of linker histones, including the abilities to bind reconstituted mononucleosomes, produce a chromatosome stop during micrococcal nuclease digestion, and aggregate chromatin. Because HILS1 is expressed in late spermatids that do not contain core histones, HILS1 may participate in spermatid nuclear condensation through a mechanism distinct from that of linker histones. Because HILS1 also belongs to the large winged helix/forkhead protein superfamily, HILS1 may also regulate gene transcription, DNA repair, and/or other chromosome processes during mammalian spermiogenesis.

Amino Acid Sequence↗
PubMed2003

Overexpression of Bcl-W in the testis disrupts spermatogenesis: revelation of a role of BCL-W in male germ cell cycle control.

To explore physiological roles of BCL-W, a prosurvival member of the BCL-2 protein family, we generated transgenic (TG) mice overexpressing Bcl-w driven by a chicken beta-actin promoter. Male Bcl-w TG mice developed normally but were infertile. The adult TG testes displayed disrupted spermatogenesis with various severities ranging from thin seminiferous epithelium containing less germ cells to Sertoli cell-only appearance. No overpopulation of any type of germ cells was observed during testicular development. In contrast, the developing TG testes displayed decreased number of spermatogonia, degeneration, and detachment of spermatocytes and Sertoli cell vacuolization. The proliferative activity of germ cells was significantly reduced during testicular development and spermatogenesis, as determined by in vivo and in vitro 5'-bromo-2'deoxyuridine incorporation assays. Sertoli cells were structurally and functionally normal. The degenerating germ cells were TUNEL-negative and no typical apoptotic DNA ladder was detected. Our data suggest that regulated spatial and temporal expression of BCL-W is required for normal testicular development and spermatogenesis, and overexpression of BCL-W inhibits germ cell cycle entry and/or cell cycle progression leading to disrupted spermatogenesis.

Animals↗
PubMed2003

Previously uncharacterized roles of platelet-activating factor acetylhydrolase 1b complex in mouse spermatogenesis.

Platelet-activating factor (PAF) has been shown to affect sperm motility and acrosomal function, thereby altering fertility. PAF acetylhydrolase 1b (PAFAH1B) hydrolyzes PAF and is composed of three subunits [the lissencephaly (LIS1) protein and alpha1 and alpha2 subunits] and structurally resembles a GTP-hydrolyzing protein. Besides the brain, transcripts for Lis1, alpha1, and alpha2 are localized to meiotic and early haploid germ cells. Here, we report disruptions of the alpha2 (Pafah1b2) and alpha1 (Pafah1b3) genes in mice. Male mice homozygous null for alpha2(alpha2-/-) are infertile, and spermatogenesis is disrupted at mid- or late pachytene stages of meiosis or early spermiogenesis. Whereas mice homozygous mutant for alpha1(alpha1-/-) have normal fertility and normal spermatogenesis, those with disruptions of both alpha1 and alpha2 (alpha1-/-alpha2-/-) manifest an earlier disturbance of spermatogenesis with an onset at preleptotene or leptotene stages of meiosis. Testicular Lis1 protein levels are up-regulated in the alpha2-/- and alpha1-/-alpha2-/- mice. Lowering Lis1 levels by inactivating one allele of Lis1 in alpha2 null or alpha1/alpha 2 null genetic backgrounds (i.e., alpha2-/-Lis1+/- or alpha1-/-alpha2-/-Lis1+/- mice) restored spermatogenesis and male fertility. Our data provide evidence for unique roles of the PAFAH1B complex and, particularly, the lissencephaly protein Lis1 in spermatogenesis.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2003

RFPL4 interacts with oocyte proteins of the ubiquitin-proteasome degradation pathway.

Oocyte meiosis and early mitotic divisions in developing embryos rely on the timely production of cell cycle regulators and their clearance via proteasomal degradation. Ret Finger Protein-Like 4 (Rfpl4), encoding a RING finger-like protein with a B30.2 domain, was discovered during an in silico search for germ cell-specific genes. To study the expression and functions of RFPL4 protein, we performed immunolocalizations and used yeast two-hybrid and other protein-protein interaction assays. Immunohistochemistry and immunofluorescence showed that RFPL4 accumulates in all growing oocytes and quickly disappears during early embryonic cleavage. We used a yeast two-hybrid model to demonstrate that RFPL4 interacts with the E2 ubiquitin-conjugating enzyme HR6A, proteasome subunit beta type 1, ubiquitin B, as well as a degradation target protein, cyclin B1. Coimmunoprecipitation analyses of in vitro translated proteins and extracts of transiently cotransfected Chinese hamster ovary (CHO)-K1 cells confirmed these findings. We conclude that, like many RING-finger containing proteins, RFPL4 is an E3 ubiquitin ligase. The specificity of its expression and these interactions suggest that RFPL4 targets cyclin B1 for proteasomal degradation, a key aspect of oocyte cell cycle control during meiosis and the crucial oocyte-to-embryo transition to mitosis.

Animals↗
PubMed2003

Apatite deposition on thermally and anodically oxidized titanium surfaces in a simulated body fluid.

By application of a special specimen set-up, thermally oxidized titanium specimen pairs were found able to deposit apatite on the contact surfaces after soaking for 7 days in the simulated body fluid (SBF) of Kokubo's recipe. The specimens oxidized at 400 degrees C and 500 degrees C showed the highest ability of apatite deposition. Both increase and decrease in oxidation temperature from this range caused the apatite deposition ability to decrease. The specimen without treatment failed to deposit any apatite. Specimens anodically oxidized in electrolytes of H(3)PO(4), H(2)SO(4) and acetic acid exhibited very low ability of apatite deposition. Furthermore, the specimen thermally oxidized at 400 degrees C was even able to help the surfaces of PTFE and silicone deposit apatite in the PTFE-Ti and silicone-Ti pairs. This in vitro experimental results indicated that the difference in apatite deposition among various titanium oxides does exist and can be distinguished by applying the present specimen set-up. The mechanism of the apatite deposition on the contact surfaces was discussed in relation to the passive dissolution of titanium in SBF. The release of titanium hydroxide and OH(-) ions from the titanium surfaces and their accumulation inside the confined space between the two contact surfaces were suggested to be responsible for the apatite deposition.

Adsorption↗
PubMed2003

Sequence and expression of testis-expressed gene 14 (Tex14): a gene encoding a protein kinase preferentially expressed during spermatogenesis.

To discover germ cell-specific genes, we used in silico subtraction and identified testis expressed gene 14 (Tex14). Mouse Tex14 contains an open reading frame encoding a 1450-amino-acid protein, which shares 64% amino acid identity with the predicted human TEX14 protein. The predicted TEX14 amino acid sequence consists of three ankyrin repeats, a protein kinase domain, and a leucine zipper dimerization motif. Northern blot analysis and in situ hybridization show that Tex14 mRNA is expressed specifically in the testis, with highest levels observed in pachytene, diplotene, and meiotically dividing spermatocytes. Two 5' splice variants of mouse Tex14 were discovered by sequencing 5'-RACE polymerase chain reaction products. TEX14 is predicted to be localized to the nucleus, suggesting that it may play a key role in regulating gene expression or modulating nuclear events during mammalian spermatogenesis.

Amino Acid Sequence↗
PubMed2003

Expression of the E3 SUMO-1 ligases PIASx and PIAS1 during spermatogenesis in the rat.

PIASx and PIAS1, two members of the conserved protein inhibitor of activated STAT (PIAS) family, are able to interact with and modulate activities of several distinct nuclear proteins, including androgen receptor (AR). PIASx and PIAS1 also function as E3-type ligases in small ubiquitin-related modifier 1 modifications. To gain better insight into the physiological roles of PIASx and PIAS1 in vivo, their cell-type specific expression and regulation were analyzed during testicular development and spermatogenesis in the rat. The expression of both PIASx and PIAS1 was low or undetectable in newborn rats. PIASx mRNA started to accumulate after day 20 of postnatal life, whereas expression of PIAS1 mRNA increased around day 30 after birth. In the adult rat testis, both PIASx and PIAS1 mRNA were present in Sertoli cells and in germ cells in the seminiferous epithelium at all stages. However, PIASx mRNA was more abundant in spermatocytes than in other cell types, whereas higher levels of PIAS1 mRNA were detected in late spermatocytes and round spermatids than in early spermatocytes. Since PIASx and PIAS1 accumulate in developing male germ cells, their regulatory functions are not only restricted to AR in Sertoli cells, but they also participate in molecular processes during meiosis.

Animals↗
PubMed2003

Genetic engineering to study testicular tumorigenesis.

In humans, Sertoli cell tumors account for approximately 4% of all testicular tumors, and 20% of these are malignant. The mechanisms underlying Sertoli cell tumorigenesis remain largely unknown. Using gene knockout technology, we previously generated mutant mice lacking the alpha subunit of inhibin dimers. The inhibin alpha-null male mice develop testicular Sertoli cell tumors with 100% penetrance. These tumors develop as early as 4 weeks of age and cause a cachexia-like wasting syndrome. Castrated inhibin alpha knockout mice develop sex steroidogenic adrenal cortical tumors. These studies have identified inhibins as secreted tumor suppressors with specificity for the gonads and adrenal glands. It had been suggested that endocrine factors play roles in Sertoli cell tumorigenesis by altering cell cycle machinery of the Sertoli cells. To test the potential of these factors to function as modifiers of Sertoli cell tumorigenesis, we have employed a genetic intercross strategy, breeding inhibin a mutant mice with mutant mice deficient in endocrine signaling factors including gonadotropin releasing hormone (hypogonadal, hpg mice), follicle stimulating hormone, anti-Miillerian hormone (AMH), activin receptor type II, or androgen receptor (testicular feminization, tfm mice), or mice overexpressing follistatin. We are also investigating the effects of loss of critical cell cycle regulators, such as cyclin dependent kinase inhibitor p27, on Sertoli cell tumorigenesis in inhibin alpha knockout males. These studies clearly demonstrate the roles of these factors as modifiers of the Sertoli cell tumorigenesis. Activin signaling through activin receptor type II is responsible for the cachexia-like syndrome observed in the inhibin a knockout mice with tumors. The gonadotropin hormones are essential for testicular tumor development, but elevated FSH levels are not sufficient to cause Sertoli cell tumors. Absence of FSH, lack of androgen receptor, or overexpression of follistatin slows the tumor growth and minimizes the cachexia symptoms, thus prolonging the life span of these double mutant mice. In contrast, absence of AMH or p27 causes earlier onset and more aggressive development of testicular tumor, with an earlier death of double mutant mice. We are currently investigating roles of estrogen signaling pathways, and other cell cycle regulators, in tumor development in the inhibin alpha knockout mice by generating mice with double or triple mutations. Genetic engineering in mouse models provides a powerful tool to study the mechanisms of testicular tumorigenesis and define the important genetic modifiers in vivo.

Activin Receptors, Type II↗
PubMed2003

The role of retinoblastoma protein family in the control of germ cell proliferation, differentiation and survival.

Retinoblastoma family proteins pRb, p107 and p130 are differentially expressed in the rat testis. They function in specific cell types during testicular development and spermatogenesis, participating in the control of proliferation, differentiation, and survival. Their expression levels and phosphorylation status are modulated during germ cell cycle progression and apoptosis. Hyperphosphorylated states and elevated levels of p107 are correlated with cell cycle progression, whereas hypophosphorylated states and reduced levels are associated with suppression of proliferation and apoptosis in germ cells and Leydig cells. These proteins may also serve as markers of cell cycle status of germ cells during spermatogenesis.

Animals↗
PubMed2003

The regulation of hepatitis C virus (HCV) internal ribosome-entry site-mediated translation by HCV replicons and nonstructural proteins.

Hepatitis C virus (HCV), the global leading cause of chronic liver disease, has a positive-sense, ssRNA genome that encodes a large polyprotein. HCV polyprotein translation is initiated by an internal ribosome-entry site (IRES) located at the 5' end of the viral genome, in a cap-independent manner, but the regulatory mechanism of this process remains poorly understood. In this study, we characterized the effect of HCV nonstructural proteins on HCV IRES-directed translation in both HCV replicon cells and transiently transfected human liver cells expressing HCV nonstructural proteins. Using bicistronic reporter gene constructs carrying either HCV or other viral IRES sequences, we found that the HCV IRES-mediated translation was specifically upregulated in HCV replicon cells. This enhancement of HCV IRES-mediated translation by the replicon cells was inhibited by treatment with either type I interferon or ribavirin, drugs that perturb HCV genome replication, suggesting that the enhancement is probably due to HCV-encoded protein function(s). Reduced phosphorylation levels of both eIF2alpha and eIF4E were observed in the replicon cells, which is consistent with our previous findings and indicates that the NS5A nonstructural protein may be involved in the regulatory mechanism(s). Indeed, transient expression of NS5A or NS4B in human liver cells stimulated HCV IRES activity. Interestingly, mutation in the ISDR of NS5A perturbed this stimulation of HCV IRES activity. All these results suggest, for the first time, that HCV nonstructural proteins preferentially stimulate the viral cap-independent, IRES-mediated translation.

Antiviral Agents↗
PubMed2003

Isolation of a novel member of small G protein superfamily and its expression in colon cancer.

AIM: APMCF1 is a novel human gene whose transcripts are up-regulated in apoptotic MCF-7 cells. In order to learn more about this gene's function in other tumors, we cloned its full length cDNA and prepared its polyclonal antibody to investigate its expression in colon cancers with immunohistochemistry. METHODS: With the method of 5' rapid amplification of cDNA end (RACE) and EST assembled in GenBank, we extended the length of APMCF1 at 5' end. Then the sequence encoding the APMCF1 protein was amplified by RT-PCR from the total RNA of apoptotic MCF-7 cells and cloned into the prokaryotic expression vector pGEX-KG to construct recombinant expression vector pGEX-APMCF1. The GST-APMCF1 fusion protein was expressed in E. coli and used to immunize rabbits to get the rabbit anti-APMCF1 serum. The specificity of polyclonal anti-APMCF1 antibody was determined by Western blot. Then we investigated the expression of Apmcf1 in colon cancers and normal colonic mucosa with immunohistochemistry. RESULTS: A cDNA fragment with a length of 1 745 bp was obtained. APMCF1 was mapped to chromosome 3q22.2 and spanned at least 14.8 kb of genomic DNA with seven exons and six introns contained. Bioinformatic analysis showed the protein encoded by APMCF1 contained a small GTP-binding protein (G proteins) domain and was homologous to mouse signal recognition particle receptor beta(SRbeta). A coding region covering 816 bp was cloned and polyclonal anti-APMCF1 antibody was prepared successfully. The immunohistochemistry study showed that APMCF1 had a strong expression in colon cancer. CONCLUSION: APMCF1 may be the gene coding human signal recognition particle receptor beta and belongs to the small-G protein superfamily. Its strong expression pattern in colon cancer suggests it may play a role in colon cancer development.

Amino Acid Sequence↗
PubMed2002

Control of PERK eIF2alpha kinase activity by the endoplasmic reticulum stress-induced molecular chaperone P58IPK.

P58(IPK) is an Hsp40 family member known to inhibit the interferon (IFN)-induced, double-stranded RNA-activated, eukaryotic initiation factor 2alpha (eIF2alpha) protein kinase R (PKR) by binding to its kinase domain. We find that the stress of unfolded proteins in the endoplasmic reticulum (ER) activates P58(IPK) gene transcription through an ER stress-response element in its promoter region. P58(IPK) interacts with and inhibits the PKR-like ER-localized eIF2alpha kinase PERK, which is normally activated during the ER-stress response to protect cells from ER stress by attenuating protein synthesis and reducing ER client protein load. Levels of phosphorylated eIF2alpha were lower in ER-stressed P58(IPK)-overexpressing cells and were enhanced in P58(IPK) mutant cells. In the ER-stress response, PKR-like ER kinase (PERK)-mediated translational repression is transient and is followed by translational recovery and enhanced expression of genes that increase the capacity of the ER to process client proteins. The absence of P58(IPK) resulted in increased expression levels of two ER stress-inducible genes, BiP and Chop, consistent with the enhanced eIF2alpha phosphorylation in the P58(IPK) deletion cells. Our studies suggest that P58(IPK) induction during the ER-stress response represses PERK activity and plays a functional role in the expression of downstream markers of PERK activity in the later phase of the ER-stress response.

Animals↗
PubMed2002

PipeOnline 2.0: automated EST processing and functional data sorting.

Expressed sequence tags (ESTs) are generated and deposited in the public domain, as redundant, unannotated, single-pass reactions, with virtually no biological content. PipeOnline automatically analyses and transforms large collections of raw DNA-sequence data from chromatograms or FASTA files by calling the quality of bases, screening and removing vector sequences, assembling and rewriting consensus sequences of redundant input files into a unigene EST data set and finally through translation, amino acid sequence similarity searches, annotation of public databases and functional data. PipeOnline generates an annotated database, retaining the processed unigene sequence, clone/file history, alignments with similar sequences, and proposed functional classification, if available. Functional annotation is automatic and based on a novel method that relies on homology of amino acid sequence multiplicity within GenBank records. Records are examined through a function ordered browser or keyword queries with automated export of results. PipeOnline offers customization for individual projects (MyPipeOnline), automated updating and alert service. PipeOnline is available at http://stress-genomics.org.

Automation↗
PubMed2002

Genomic structures of the human and murine corin genes and functional GATA elements in their promoters.

Corin is a multiple-domain type II transmembrane serine protease highly expressed in the heart. It converts pro-atrial natriuretic peptide to atrial natriuretic peptide, a cardiac hormone that regulates blood volume and pressure. Here we describe the genomic structures of the human and murine corin genes and functional analysis of their promoters. Both corin genes contain 22 exons and span >200 kb. Their intron/exon boundaries are well conserved, with most exons encoding distinct structural domains, supporting the idea that corin evolved as a result of exon duplication and rearrangement. Comparison of the 5'-flanking regions of the human and murine corin genes revealed several conserved sequences, including binding sites for TBX5, GATA, NKX2.5, and Krüppel-like transcription factors. Transfection experiments with reporter gene constructs driven by the human or murine corin 5'-flanking region indicated that the sequences from -405 to -15 in human and from -646 to -77 in mouse are sufficient to promote high levels of gene expression in murine cardiomyocytes. In contrast, these sequences produced only minimal levels of expression in HeLa cells. Within these sequences, we identified a conserved GATA element that bound to GATA-4. Mutation of the core sequence impaired both GATA-4 binding and gene expression. These data indicate that the GATA element and its binding to GATA-4 are essential for cardiac expression of the human and murine corin genes.

Animals↗
PubMed2002

Matrix protein gene expression in intervertebral disc cells subjected to altered osmolarity.

Physiologic loading of the intervertebral disc may lead to changes in the osmotic pressure experienced by the resident cells. In this study, changes in gene expression levels for extracellular matrix and cytoskeletal proteins were quantified in disc cells subjected to hypo-osmotic (255 mOsm) or hyper-osmotic conditions (450 mOsm), relative to iso-osmotic conditions (293 mOsm). Important differences were observed in osmolarity and between cells of different regions, corresponding to the transition zone and nucleus pulposus. Under hypo-osmotic conditions, gene expressions for aggrecan and type II collagen were up-regulated in the transition zone, but not in the nucleus pulposus cells. Genes for the small proteoglycans, biglycan, and decorin, but not lumican, were up-regulated in transition zone cells following incubation in either hypo- or hyper-osmotic media. The same genes were down-regulated in nucleus pulposus cells under either hypo- or hyper-osmotic conditions. Differences in the response to altered osmolarity between cells of the intervertebral disc may relate to their different cytoskeletal structures or embryological origins.

Alginates↗