Biomedical subjects

Mingyao Liu

Publications and source records attributed to Mingyao Liu.

At least 19 recordsLinked to original sources

PubMed2007

GCIP/CCNDBP1, a helix-loop-helix protein, suppresses tumorigenesis.

Deletions and/or loss of heterozygosity (LOH) on chromosome 15 (15q15 and 15q21) have been found in several human tumors, including carcinomas of the colorectum, breast, lung, prostate, and bladder, suggesting the presence of potential tumor suppressor gene(s) in this particular region of chromosome 15. GCIP also called CCNDBP1, DIP1, or HHM, localized at chromosome 15q15, is a recently identified helix-loop-helix leucine zipper (HLH-ZIP) protein without a basic region like the Id family of proteins. In this study, we reported that the expression of GCIP was significantly downregulated in several different human tumors, including breast tumor, prostate tumor, and colon tumors. In human colon tumors, both mRNA and protein expression levels of GCIP were decreased significantly compared to the normal tissues. Treatment of colon cancer cells SW480 with sodium butyrate (NaB), which induces colon cancer cell differentiation, can induce the upregulation of GCIP expression, suggesting that the protein functions as a negative regulator in cell proliferation. Overexpression of GCIP in SW480 colon cancer cell line resulted in a significant inhibition on tumor cell colony formation, while silencing of GCIP expression by siRNA can promote cell colony formation. Furthermore, overexpression of GCIP inhibited the transcriptional activity of cyclin D1 promoter and the expression of cyclin D1 protein in the cell. Finally, we demonstrate that GCIP specifically interacts with one of the class III HDAC proteins, SirT6, which is important for maintaining genome stability. Together, our data suggest a possible function of GCIP in tumor suppression.

Animals↗

PubMed2007

Transforming growth factor-beta-independent regulation of myogenesis by SnoN sumoylation.

Recent progress has been made on the role of oncoproteins c-Ski and related SnoN in the control of cellular transformation. c-Ski/SnoN potently repress transforming growth factor-beta (TGF-beta) antiproliferative signaling through physical interaction with signal transducers called Smads. Overexpression of c-Ski/SnoN also induces skeletal muscle differentiation, but how c-Ski/SnoN function in myogenesis is largely unknown. During our investigation on the role of sumoylation in TGF-beta signaling, we inadvertently found that SnoN is modified by small ubiquitin-like modifier-1 (SUMO-1). Here, we biochemically characterize SnoN sumoylation in detail and report the physiological function of the modification. Sumoylation occurs primarily at lysine 50 (Lys-50). PIAS1 and PIASx proteins physically interact with SnoN to stimulate its sumoylation, thus serving as SUMO-protein isopeptide ligases (E3) for SnoN sumoylation. SnoN sumoylation does not alter its metabolic stability or its ability to repress TGF-beta signaling. Notably, loss of sumoylation in the Lys-50 site (via a Lys-to-Arg point mutation) potently activates muscle-specific gene expression and enhances myotube formation. Our study suggests a novel role for SUMO modification in the regulation of myogenic differentiation.

Cell Line↗

PubMed2006

Cloning and expression of a novel human gene, Isl-2, encoded a LIM-homeodomain protein.

The LIM-homeodomain (LIM-HD) proteins have a homeodomain and two N-terminal LIM domains, which consist of a conserved cysteine- and histidine-rich structure of two tandem repeated zinc fingers. LIM domain is involved in protein-protein interactions during transcriptional regulation. LIM-HD proteins are classically suggested as major transcriptional regulators which, in cooperation with other transcription factors, play critical roles in several developing systems and organs, such as nervous system, pancreas, and heart. Here we have cloned the full-length cDNA of human Isl-2 from a human embryo heart cDNA library. The gene contains six exons and spans 5.7 kb in chromosome 15q23 region, and transcribes a 1.9 kb mRNA that encodes a protein with 359 amino acid residues. The predicted protein, containing two tandem LIM motifs in N-terminal and a homeodomain domain, is well conserved, especially in the LIM and DNA-binding domains. Northern blot analysis shows that human Isl-2 is expressed in every human tissue examined at adult stage and during embryonic developmental stages from 34 days to 24 weeks at different levels in tissues. The broad expression of Isl-2 gene in tissues during embryogenesis and adult development suggests that it may be involved in both differentiation and maintenance of these tissues and might play an important role.

Amino Acid Sequence↗

PubMed2006

A novel human gene ZNF415 with five isoforms inhibits AP-1- and p53-mediated transcriptional activity.

The zinc finger proteins are the single largest class of transcription factors in human genome. Previous studies revealed that zinc finger proteins are involved in transcriptional activation and regulation of apoptosis, etc. Alternative splicing emerges as a major mechanism of generating protein diversity and many zinc finger proteins reported have isoforms. In this article, we identify and characterize five isoforms of a novel zinc finger gene named ZNF415; these five isoforms were named ZNF415-1 to ZNF415-5. The five isoforms display different subcellular localization and are expressed at different levels in both embryonic and adult tissues. Furthermore, the splicing variants of ZNF415 display different transcriptional activity. Except for ZNF415-1, overexpression of the other ZNF415 isoforms in COS-7 cells inhibits the transcriptional activities of AP-1 and p53, suggesting that the ZNF415 protein may be involved in AP-1- and p53-mediated transcriptional activity.

Animals↗

PubMed2006

Cell-based tissue engineering for lung regeneration.

Emphysema is a chronic lung disease characterized by alveolar enlargement and tissue loss. Tissue engineering represents an attractive potential for regeneration of several organ systems. The complex three-dimensional architectural structure of lung parenchyma requiring connections of alveolar units to airways and the pulmonary circulation makes this strategy less optimistic. In the present study, we used Gelfoam sponge as a scaffold material, supplemented with fetal rat lung cells as progenitors, to explore the potential application of cell-based tissue engineering for lung regeneration in adult rats. After injection into lung parenchyma, the sponge showed porous structures similar to alveolar units. It did not induce severe local inflammatory response. Fetal lung cells in the sponge were able to survive in the adult lung for at least 35 days, determined by CMTMR [5-(and-6)-{[(4-chloromethyl)benzoyl]amino}tetramethylrhodamine] labeling. Proliferation of cells within the sponge was demonstrated in vivo by bromodeoxyuridine (BrdU) labeling. Cells formed "alveolar-like structures" at the border between the sponge and the surrounding lung tissue with positive immunohistochemical staining for epithelial and endothelial cells. Neovascularization of the sponge was demonstrated with India ink perfusion. The sponge degraded after several months. This study suggests that cell-based tissue engineering possesses the potential to regenerate alveolar-like structures, an important step towards our ultimate goal of lung regeneration.

Absorbable Implants↗

PubMed2006

High-volume ventilation induces pentraxin 3 expression in multiple acute lung injury models in rats.

Pentraxin 3 (PTX3) is an acute-phase protein, which can be produced by a variety of tissue cells at the site of infection or inflammation. It plays an important role in innate immunity in the lung and in mediating acute lung injury. The aim of this study was to determine the effect of mechanical ventilation on PTX3 expression in multiple lung injury models. Male Sprague-Dawley rats were challenged with intravenous injection of lipopolysaccharide (LPS) or hemorrhage followed by resuscitation (HS). The animals were then subjected to either relatively higher (12 ml/kg) or lower (6 ml/kg, positive end-expiratory pressure of 5 cmH(2)O) volume ventilation for 4 h. High-volume ventilation significantly enhanced PTX3 expression in the lung, either alone or in combination with LPS or hemorrhage. A significant increase of PTX3 immunohistochemistry staining in the lung was seen in all injury groups. The PTX3 expression was highly correlated with the severity of lung injury determined by blood gas, lung elastance, and wet-to-dry ratio. To determine the effects of HS, LPS, or injurious ventilation (25 ml/kg) alone on PTX3 expression, another group of rats was studied. Injurious ventilation significantly damaged the lung and increased PTX3 expression. A local expression of PTX3 induced by high-volume ventilation, either alone or in combination with other pathological conditions, suggests that it may be an important mediator in ventilator-induced lung injury.

Acute Disease↗

PubMed2006

A novel human zinc finger protein ZNF540 interacts with MVP and inhibits transcriptional activities of the ERK signal pathway.

Mitogen-activated protein kinases (MAPKs) are evolutionarily conserved enzymes in cell signal transduction. Previous studies revealed that zinc finger proteins are involved in the regulation of the MAPK signaling pathways. Here we report the identification and characterization of a novel human zinc finger protein, ZNF540. The cDNA of ZNF540 is 3.3kb, encoding 660 amino acids in the nucleus and the cytoplasm. Northern blot analysis indicates that ZNF540 is expressed in most of the fetal tissues. Overexpression of FLAG-ZNF540 in COS-7 cells represses the transcriptional activities of SRE and ELK-1, which can be relieved by siRNA. MVP, one of MAPK scaffold proteins, is identified as a potential ZNF540-binding protein. This interaction is detected by a yeast two-hybrid assay, reporter gene assays, and co-immunoprecipitation. Taken together, these results suggest that ZNF540 may act as a transcriptional repressor in MAPK signaling pathway to mediate cellular functions.

Amino Acid Sequence↗

PubMed2006

ZNF325, a novel human zinc finger protein with a RBaK-like RB-binding domain, inhibits AP-1- and SRE-mediated transcriptional activity.

Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of eukaryotic cell regulation. The zinc-finger-containing transcription factors have been previously revealed to be involved in the regulation of the MAPK signaling pathways. Here, we have identified a novel human zinc-finger transcriptional repressor, ZNF325, that contains a RBaK-like RB-binding domain and 15 tandem repeated C2H2 type zinc fingers. Northern blot analysis indicates that a 2.7 kb transcript specific for ZNF325 is widely expressed in all tissues examined at adult stage and in most of the embryonic tissues. Overexpression of ZNF325 in COS-7 cells inhibits the transcriptional activities of AP-1 and SRE. The deletion and RNAi analysis indicate that the C2H2 zinc finger motifs represent the basal transcriptional repressive activity. These results indicate that the ZNF325 protein may act as a novel transcription repressor in MAPK signaling pathway to mediate cellular functions.

Amino Acid Sequence↗

PubMed2006

The prostate-specific G-protein coupled receptors PSGR and PSGR2 are prostate cancer biomarkers that are complementary to alpha-methylacyl-CoA racemase.

BACKGROUND: Immunohistochemistry (IHC) to detect alpha-methylacyl-CoA racemase (AMACR) expression can be useful in the diagnosis of small foci of prostate cancer on needle biopsy specimens, although it still has limitations in terms of both sensitivity and specificity. We have previously described the increased expression of two prostate-specific G-protein coupled receptors (PSGR and PSGR2) in human prostate cancer. To examine their potential usefulness as cancer biomarkers, we have evaluated their expression relative to AMACR in prostate cancer tissues. METHODS: Expression of PSGR, PSGR2, and AMACR were examined by quantitative reverse-transcriptase PCR in mRNAs from benign prostate and prostate cancer tissues. Expression of PSGR2 and AMACR was also examined by in situ hybridization using a prostate cancer tissue microarray. RESULTS: By in situ hybridization, 24 of 40 prostate cancer cases showed concordant expression of PSGR2 and AMACR. However, in 16 cases there was significant discordance between expression levels of these two markers. By quantitative RT-PCR all three markers were substantially increased in cancer, with AMACR the most overexpressed (30-fold), followed by PSGR2 (13-fold) and PSGR (10-fold). AMACR was the best single marker of prostate cancer but in 7 of the 59 total cases the expression of AMACR was not significantly elevated while PSGR and/or PSGR2 were substantially elevated. CONCLUSION: All three biomarkers are increased in prostate cancer but their expression is not completely concordant. There is a subset of cases in which analysis of expression of PSGR and/or PSGR2, in addition to AMACR, would be diagnostically useful.

Biomarkers, Tumor↗

PubMed2006

ZNF569, a novel KRAB-containing zinc finger protein, suppresses MAPK signaling pathway.

Transcription factors play an essential role in altering gene expression. A great progress about transcription factors has been made towards the understanding of normal physiological processes, embryonic development, and human diseases. Here we report the identification and characterization of a novel KRAB-containing zinc-finger protein, ZNF569, which is isolated from a human embryonic heart cDNA library. ZNF569 encodes a putative protein of 686 amino acids. The protein is conserved across different species during evolution. Expression of ZNF569 was found in most of the examined human adult and embryonic tissues with a higher level in heart and skeletal muscles. The KRAB and ZNF motifs of ZNF569 represent potent repression domains. When ZNF569 is fused to Gal-4 DNA-binding domain and co-transfected with VP-16, ZNF569 protein suppresses transcriptional activity. Overexpression of ZNF569 in COS-7 cells inhibited the transcriptional activities of SRE and AP-1, which may be silenced by siRNA. The results suggest that ZNF569 protein may act as a transcriptional repressor that suppresses MAPK signaling pathway to mediate cellular functions.

Amino Acid Motifs↗

PubMed2006

The Rho-family guanine nucleotide exchange factor GEFT enhances retinoic acid- and cAMP-induced neurite outgrowth.

The Rho GTPases are important regulators of neurite outgrowth and pathfinding. We have recently reported that a Rho-family guanine nucleotide exchange factor, GEFT, modulates dendrite spine morphology and basal neurite outgrowth in primary hippocampal neurons and Neuro2A cells, respectively. Here we demonstrate that GEFT protein is highly expressed in all regions of the brain and is highly up-regulated upon treatment of Neuro2A cells with retinoic acid and dibutyric cAMP, which promote dendrite and axon-like neurite extensions, respectively. Within retinoic acid-induced neurite extensions, GEFT is localized to actin-enriched regions in the primary neurites, with little or no expression from secondary branches. Dibutyric cAMP-induced neurite extensions are highly concentrated for GEFT at the actin-rich distal tip of the growth cone. Additionally, we demonstrate that GEFT promotes neurite outgrowth in undifferentiated as well as differentiated Neuro2A cells. Together, our data provide new evidence suggesting that GEFT is an important regulator of multiple processes involved in axon and dendrite formation.

Actins↗

PubMed2006

The effect of gender combinations on outcome in human lung transplantation: the International Society of Heart and Lung Transplantation Registry experience.

BACKGROUND: In the current practice of lung transplantation, donor and recipient genders are neither directly considered nor matched. METHODS: We analyzed the potential effect of gender combinations on survival in 9,651 lung transplant recipients in the International Society of Heart and Lung Transplantation Registry (ISHLT) Registry. We compared the risk of overall and 90-day mortality by using statistical models that accounted for confounding variables. RESULTS: A Kaplan-Meier survival analysis revealed a significant difference of survival among gender combinations (log rank, p = 0.0009). The unadjusted odds ratio (OR) of 90-day mortality was significantly higher in female (F) donors to male (M) recipients (OR, 1.58; 95% confidence interval (CI), 1.22-2.04; p < 0.001) and lower in F to F (OR, 0.742; 95% CI, 0.61-0.90; p = 0.004) compared with the reference category of M to M. After adjusting for size mismatch and diagnosis in the multivariate logistic regression model, the OR of F to M was still statistically significant (F to M OR, 1.52l; 95% CI, 1.04-2.20; p = 0.028; F to F OR, 0.67; 95% CI, 0.53-0.91; p = 0.008) for 90-day mortality. A Cox proportional hazards analysis for overall survival also showed a significantly higher hazard ratio of 1.12 in F to M (95% CI, 1.01-1.23) and a lower hazard ratio of 0.92 in F to F (95% CI, 0.87-0.98). CONCLUSION: ISHLT Lung Transplant Registry data demonstrated a significant risk for F to M. Interestingly, F to F appears to be potentially beneficial in lung transplantation. Gender combinations do appear to significantly impact outcome after lung transplantation.

Adult↗

PubMed2006

Src protein tyrosine kinase family and acute inflammatory responses.

Acute inflammatory responses are one of the major underlying mechanisms for tissue damage of multiple diseases, such as ischemia-reperfusion injury, sepsis, and acute lung injury. By use of cellular and molecular approaches and transgenic animals, Src protein tyrosine kinase (PTK) family members have been identified to be essential for the recruitment and activation of monocytes, macrophages, neutrophils, and other immune cells. Src PTKs also play a critical role in the regulation of vascular permeability and inflammatory responses in tissue cells. Importantly, animal studies have demonstrated that small chemical inhibitors for Src PTKs attenuate tissue injury and improve survival from a variety of pathological conditions related to acute inflammatory responses. Further investigation may lead to the clinical application of these inhibitors as drugs for ischemia-reperfusion injury (such as stroke and myocardial infarction), sepsis, acute lung injury, and multiple organ dysfunction syndrome.

Animals↗

PubMed2006

PSGR2, a novel G-protein coupled receptor, is overexpressed in human prostate cancer.

The G-protein coupled receptors (GPCRs) recognize a large variety of extracellular molecules (such as hormones, neurotransmitters, growth and developmental factors) and several sensory messages (such as light, odors and pain). GPCRs and their signal transduction pathway represent important specific targets for a variety of human diseases. To investigate the potential roles of GPCRs in human normal prostate and prostate cancers, we identified and characterized a novel human G-protein coupled receptor, PSGR2, which is highly overexpressed in human prostate cancers. Although PSGR2 shares sequence homology with human olfactory G-protein coupled receptors, the expression of PSGR2 is highly restricted to human prostate tissue, and no expression was detected in 22 normal and 10 tumor tissues examined using Northern blot and PCR analysis. Furthermore, we investigated the expression levels of PSGR2 in 133 human prostate samples with real-time quantitative reverse transcription-PCR and in situ hybridization method. We demonstrated that PSGR2 expression increased significantly in human high grade prostate intraepithelial neoplasia (PIN) and prostate cancers (approximately 10-fold) as compared to normal and BPH (benign prostatic hyperplasia) tissues (p < 0.001), suggesting PSGR2 may play an important role in human prostate cancer development and progression. Together, our results suggest that PSGR2 is a novel prostate specific G-protein coupled receptor and may be useful as a tissue marker and molecular target for the early detection and treatment of human prostate cancers.

Amino Acid Sequence↗

PubMed2006

hnulp1, a basic helix-loop-helix protein with a novel transcriptional repressive domain, inhibits transcriptional activity of serum response factor.

Many bHLH proteins are involved in cardiac development and cardiovascular diseases. Herein, we identified and characterized the human homologue (hnulp1) of mouse gene nulp1. The predicted protein contains a bHLH domain and a DUF654 domain in N-terminal and C-terminal, respectively. Northern blot analysis shows that a 2.3-kb transcript expressed broadly in early human embryonic and adult tissues, especially with a higher level in adult heart. hnulp1 is a transcription repressor when fused to GAL4 DNA-binding domain and co-transfected with VP-16, in which DUF654 motif represents the basal transcriptional repressive activity. Treatment of cells with trichostatin A can relieve this repression, suggesting that the DUF654 motif acts through increasing deacetylase activity at the GAL4-driven promoter. Overexpression of hnulp1 protein in COS-7 cells inhibits the transcriptional activity of serum response factor (SRF), suggesting that hnulp1 may act as a novel bHLH transcriptional repressor in SRF signaling pathway to mediate cellular functions.

Amino Acid Sequence↗

PubMed2006

Lipopolysaccharide accelerates caspase-independent but cathepsin B-dependent death of human lung epithelial cells.

Caspase-independent cell death has drawn increasing attention. In the present study, we found that lipopolysaccharide (LPS) accelerated spontaneous death of human lung epithelial A549 cells in a serum- and cell density-dependent manner: while serum starvation has been demonstrated to induce apoptosis in the same cell line, LPS-induced cell death was only observed in the presence of serum; in addition, the cell death was not observed when the cells were seeded at 10- or 100-fold lower density. The apoptotic features were demonstrated by TUNEL assay, DNA laddering and Annexin V staining. However, treatment of cells with two commonly used pan-caspase inhibitors, zVAD.fmk or BOC-D.fmk, failed to block cell death. In contrast, two cathepsin B inhibitors, Ca074-Me or N-1845, reduced cell death significantly. A time-dependent activation of cathepsin B, but not caspase 3, was observed in both control and LPS-treated cells. Although LPS did not further activate cathepsin B or its release, it increased expression and translocation of apoptosis inducing factor from mitochondria to the nucleus, and increased release of cytochrome c from mitochondria. LPS-induced cell death was significantly attenuated by either N-acetyl-L-cysteine or pyrrolidine-dithiocarbamate, both free radical scavengers. Disruption of lipid raft formation with filipin or methyl-beta-cyclodextrin also reduced apoptosis significantly, suggesting that lipid raft-dependent signaling is essential. These data imply that confluent cells undergo spontaneous cell death mediated by cathepsin B; LPS may accelerate this caspase-independent cell death through release of mitochondrial contents and reactive oxygen species.

Caspase 3↗

PubMed2006

Toll-like receptor and cytokine gene expression in the early phase of human lung transplantation.

BACKGROUND: Innate immunity is the first line of host defense against invading microorganisms, which is mediated by specific pathogen recognition molecules called toll-like receptors (TLRs). TLRs can also recognize endogenous "danger" signals, resulting in cytokine production and activation of the adaptive immune system. We hypothesized that gene expression of TLRs during lung transplantation may be affected by the donor condition and the ischemia-reperfusion process, which may subsequently influence graft function. METHODS: Lung biopsies from 14 patients were collected before and after reperfusion, and mRNA levels of TLRs, cytokines (interleukin [IL]-1beta, IL-6, IL-8, IL-10 and interferon-gamma) and heat-shock protein 70 (HSP70) were measured by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: In cold-preserved donor lungs, all TLRs (except TLR3) showed significant correlations with one another and also with the cytokines examined. Expression of several TLRs and cytokines correlated with the intubation time of donors. TLR4 gene expression correlated closely with IL-8 before and after reperfusion (p </= 0.01). After reperfusion, HSP70 mRNAs increased significantly (p < 0.05). CONCLUSIONS: Differential expression levels of TLRs and cytokine genes likely reflect the inflammatory status of lung grafts; correlation of TLR genes with cytokine genes and clinical conditions implicates a potential role of TLRs in early graft responses.

Adult↗

PubMed2006

Lung regeneration: implantation of fetal rat lung fragments into adult rat lung parenchyma.

OBJECTIVE: The capability of regeneration of lung tissues in adults is limited after chronic destruction. Bone marrow-derived stem cells, retinoic acid, growth factors, and other approaches have been attempted to promote or facilitate this process. We hypothesized that fetal lung tissues, with great potential for growth and differentiation, could be used for lung regeneration. METHODS: Day 17 fetal lung tissue fragments at the pseudoglandular stage of lung development from Lewis rats were implanted into adult Lewis rat lungs. For group 1, fetal lung fragments were injected into the adult left lung parenchyma; for group 2, fetal fragments were injected with the left lung partially resected; for group 3, adult fragments were injected; and for groups 4 and 5, fetal fragments were implanted into the omentum and subcutaneous tissue, respectively. RESULTS: The grafts implanted into pulmonary parenchyma were differentiated with opening of the alveolar space after 4 weeks and were advanced further with morphologic features similar to those of neonatal lungs after 8 and 12 weeks. The implants were connected with pulmonary circulation determined by means of perfusion with India ink. These changes appeared to be further enhanced in animals with partial lung resection that might have facilitated the maturation of implanted fetal lung tissues through mechanical factors, soluble factors, or both. Fetal lung tissues did not mature when implanted into the omentum or subcutaneous tissue. Adult lung fragments did not expand after being reimplanted back into the same animal. CONCLUSIONS: Fetal lung tissue might be an option for further investigation into lung regeneration.

Age Factors↗