Mesenchymal Stem Cells Mediated Suppression of GREM2 Inhibits Renal Epithelial-Mesenchymal Transition and Attenuates the Progression of Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide. Despite advancements in various treatments, the prevalence of DKD continues to rise, leading to a significant increase in the demand for dialysis and kidney transplantation. This study aimed to evaluate the effects of a Small cell＋Ultra Potent＋Scale UP cell (SMUP-Cell), a type of human umbilical cord blood-derived mesenchymal stem cell, on DKD in the db/db mouse model of type 2 diabetes mellitus.

Sphingosine 1-Phosphate Receptor 4 Promotes Nonalcoholic Steatohepatitis by Activating NLRP3 Inflammasome.

Background & Aims: Sphingosine 1-phosphate receptors (S1PRs) are a group of G-protein-coupled receptors that confer a broad range of functional effects in chronic inflammatory and metabolic diseases. S1PRs also may mediate the development of nonalcoholic steatohepatitis (NASH), but the specific subtypes involved and the mechanism of action are unclear.

Methods: We investigated which type of S1PR isoforms is activated in various murine models of NASH.

Sphingomyelin synthase 1 mediates hepatocyte pyroptosis to trigger non-alcoholic steatohepatitis.

Objective: Lipotoxic hepatocyte injury is a primary event in non-alcoholic steatohepatitis (NASH), but the mechanisms of lipotoxicity are not fully defined. Sphingolipids and free cholesterol (FC) mediate hepatocyte injury, but their link in NASH has not been explored. We examined the role of free cholesterol and sphingomyelin synthases (SMSs) that generate sphingomyelin (SM) and diacylglycerol (DAG) in hepatocyte pyroptosis, a specific form of programmed cell death associated with inflammasome activation, and NASH.

Mitophagy deficiency increases NLRP3 to induce brown fat dysfunction in mice.

Although macroautophagy/autophagy deficiency causes degenerative diseases, the deletion of essential autophagy genes in adipocytes paradoxically reduces body weight. Brown adipose tissue (BAT) plays an important role in body weight regulation and metabolic control. However, the key cellular mechanisms that maintain BAT function remain poorly understood.

Developmentally regulated GTP-binding protein 2 depletion leads to mitochondrial dysfunction through downregulation of dynamin-related protein 1.

Mitochondrial dynamics, including constant fusion and fission, play critical roles in maintaining mitochondrial morphology and function. Here, we report that developmentally regulated GTP-binding protein 2 (DRG2) regulates mitochondrial morphology by modulating the expression of the mitochondrial fission gene dynamin-related protein 1 (Drp1). shRNA-mediated silencing of DRG2 induced mitochondrial swelling, whereas expression of an shRNA-resistant version of DRG2 decreased mitochondrial swelling in DRG2-depleted cells.

Protective role of endogenous plasmalogens against hepatic steatosis and steatohepatitis in mice.

Unlabelled: Free cholesterol (FC) accumulation in the liver is an important pathogenic mechanism of nonalcoholic steatohepatitis (NASH). Plasmalogens, key structural components of the cell membrane, act as endogenous antioxidants and are primarily synthesized in the liver. However, the role of hepatic plasmalogens in metabolic liver disease is unclear.

Statins Increase Mitochondrial and Peroxisomal Fatty Acid Oxidation in the Liver and Prevent Non-Alcoholic Steatohepatitis in Mice.

Background: Non-alcoholic fatty liver disease is the most common form of chronic liver disease in industrialized countries. Recent studies have highlighted the association between peroxisomal dysfunction and hepatic steatosis. Peroxisomes are intracellular organelles that contribute to several crucial metabolic processes, such as facilitation of mitochondrial fatty acid oxidation (FAO) and removal of reactive oxygen species through catalase or plasmalogen synthesis.

Nitric Oxide Produced by Macrophages Inhibits Adipocyte Differentiation and Promotes Profibrogenic Responses in Preadipocytes to Induce Adipose Tissue Fibrosis.

Fibrosis of adipose tissue induces ectopic fat accumulation and insulin resistance by inhibiting adipose tissue expandability. Mechanisms responsible for the induction of adipose tissue fibrosis may provide therapeutic targets but are poorly understood. In this study, high-fat diet (HFD)-fed wild-type (WT) and iNOS(-/-) mice were used to examine the relationship between nitric oxide (NO) produced by macrophages and adipose tissue fibrosis.

Developmentally regulated GTP-binding protein 2 coordinates Rab5 activity and transferrin recycling.

The small GTPase Rab5 regulates the early endocytic pathway of transferrin (Tfn), and Rab5 deactivation is required for Tfn recycling. Rab5 deactivation is achieved by RabGAP5, a GTPase-activating protein, on the endosomes. Here we report that recruitment of RabGAP5 is insufficient to deactivate Rab5 and that developmentally regulated GTP-binding protein 2 (DRG2) is required for Rab5 deactivation and Tfn recycling.

11β-HSD1 reduces metabolic efficacy and adiponectin synthesis in hypertrophic adipocytes.

Mitochondrial dysfunction in hypertrophic adipocytes can reduce adiponectin synthesis. We investigated whether 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) expression is increased in hypertrophic adipocytes and whether this is responsible for mitochondrial dysfunction and reduced adiponectin synthesis. Differentiated 3T3L1 adipocytes were cultured for up to 21 days.

NRP-1 expression is strongly associated with the progression of pituitary adenomas.

The purpose of the present study was to identify a predictive marker associated with tumor progression or recurrence. We investigated the expression of p53, Ki-67, Bax, Bcl-2, vascular endothelial growth factor (VEGF)-A, VEGFR-1, VEGFR-2 and neuropilin-1 (NRP-1) in pituitary adenomas (PAs) with/without tumor progression during follow-up periods. We compared the expression of these molecules in primary and recurrent specimens to identify a predictive marker associated with tumor progression.

Developmentally regulated GTP-binding protein 2 ameliorates EAE by suppressing the development of TH17 cells.

Developmentally regulated GTP-binding protein 2 (DRG2) represents a novel subclass of GTP-binding proteins. We here report that transgenic overexpression of DRG2 in mice ameliorates experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). The protective effect of DRG2 in EAE was mediated by the inhibition of the development of T(H)17 cells.

Mitochondrial dysfunction and activation of iNOS are responsible for the palmitate-induced decrease in adiponectin synthesis in 3T3L1 adipocytes.

Mitochondrial dysfunction and endoplasmic reticulum (ER) stress are considered the key determinants of insulin resistance. Impaired mitochondrial function in obese animals was shown to induce the ER stress response, resulting in reduced adiponectin synthesis in adipocytes. The expression of inducible nitric oxide synthase (iNOS) is increased in adipose tissues in genetic and dietary models of obesity.

A nuclear localization of the infectious haematopoietic necrosis virus NV protein is necessary for optimal viral growth.

The nonvirion (NV) protein of infectious hematopoietic necrosis virus (IHNV) has been previously reported to be essential for efficient growth and pathogenicity of IHNV. However, little is known about the mechanism by which the NV supports the viral growth. In this study, cellular localization of NV and its role in IHNV growth in host cells was investigated.

Tristetraprolin mediates anti-inflammatory effects of nicotine in lipopolysaccharide-stimulated macrophages.

Nicotine inhibits the release of TNF-α from macrophage through activation of STAT3. Tristetraprolin (TTP) is known to destabilize pro-inflammatory transcripts containing AU-rich elements (ARE) in 3'-untranslated region (3'-UTR). Here we show that in LPS-stimulated human macrophages the anti-inflammatory action of nicotine is mediated by TTP.

Casein kinase 2 regulates the mRNA-destabilizing activity of tristetraprolin.

Tristetraprolin (TTP) is an AU-rich element-binding protein that regulates mRNA stability. We previously showed that TTP acts as a negative regulator of VEGF gene expression in colon cancer cells. The p38 MAPK pathway is known to suppress the TTP activity.

Transcription factor Sp1 regulates basal transcription of the human DRG2 gene.

Developmentally regulated GTP-binding protein 2 (DRG2) is an evolutionarily conserved GTP-binding protein. DRG2 mRNA expression has been confirmed in many animal and human tissues. DRG2 is thought to play an essential role in the control of cell growth and differentiation.

Stability of the LATS2 tumor suppressor gene is regulated by tristetraprolin.

LATS2 is a tumor suppressor gene implicated in the control of cell growth and the cell cycle. Here, we investigated the post-transcriptional regulation of LATS2 expression by tristetraprolin (TTP). Our results show that the expression level of LATS2 is inversely correlated with TTP expression in human cancer cell lines.

NF-kappaB activation is required for cisplatin-induced apoptosis in head and neck squamous carcinoma cells.

This study demonstrates a requirement for NF-kappaB activation in cis-diamminedichloroplatinum (cisplatin)-induced apoptosis in human head and neck squamous cell carcinoma (HNSCC) cell lines. This conclusion was supported by the following observations: cisplatin induced IkappaBalpha degradation and NF-kappaB-dependent transcriptional activation prior to cell death; pyrrolidine dithiocarbamate (PDTC), a chemical inhibitor of NF-kappaB activation, prevented apoptosis; lactacystin, an inhibitor of IkappaBalpha degradation, also prevented apoptosis; and finally, the expression of a super-repressor mutant IkappaBalpha blocked apoptosis. The expression of tumor necrosis factor alpha (TNFalpha) was promoted by cisplatin treatment and was suppressed by PDTC treatment.

Heat shock 70-kDa protein 8 isoform 1 is expressed on the surface of human embryonic stem cells and downregulated upon differentiation.

The cell-surface markers used routinely to define the undifferentiated state and pluripotency of human embryonic stem cells (hESCs) are those used in mouse embryonic stem cells (mESCs) because of a lack of markers directly originated from hESC itself. To identify more hESC-specific cell-surface markers, we generated a panel of monoclonal antibodies (MAbs) by immunizing the irradiated cell clumps of hESC line Miz-hES1, and selected 26 MAbs that were able to bind to Miz-hES1 cells but not to mESCs, mouse embryonic fibroblast cells, and STO cells. Most antibodies did not bind to human neural progenitor cells derived from the Miz-hES1 cells, either.

Complete genomic DNA sequence of rock bream iridovirus.

Iridovirus is a causative agent of epizootics among cultured rock bream (Oplegnathus fasciatus) in Korea. Here, we report the complete genomic sequence of rock bream iridovirus (RBIV). The genome of RBIV was 112080 bp long and contained at least 118 putative open reading frames (ORFs), and its genome organization was similar to that of infectious spleen and kidney necrosis virus (ISKNV).

Overexpression of DRG2 increases G2/M phase cells and decreases sensitivity to nocodazole-induced apoptosis.

DRG2, a member of the DRG subfamily in the GTP-binding protein superfamily, was identified as a repressed gene product in fibroblasts transformed by SV40. The significance of this down-regulation and the cellular role of DRG2 has not been understood in the past. To investigate the function of DRG2 we made a Jurkat cell line, Jurkat-LNCX2-DRG2, stably transfected with pLNCX2-DRG2 to overexpress human DRG2.

Overexpression of DRG2 suppresses the growth of Jurkat T cells but does not induce apoptosis.

Developmentally regulated GTP-binding protein (DRG) is a new subfamily within the superfamily of GTP-binding proteins. Its expression is regulated during embryonic development. To investigate the effect of the expression of DRG2 on cell growth, we constructed a human Jurkat-T-cell line that overexpresses DRG2.

Highly conserved sequences of three major virion proteins of a Korean isolate of white spot syndrome virus (WSSV).

In Korea, mass mortality occurred among cultured shrimp with visible macroscopic white spots in 2000, and we confirmed the presence of white spot syndrome virus (WSSV) in the tissues of moribund shrimp by electron microscopy. In order to identify the characteristics of this Korean isolate of WSSV, we cloned and characterized its genomic DNA coding for VP24, VP26, and VP28. On the nucleotide level, VP24, VP26, and VP28 of the Korean isolate were found to be 100%, 100%, and 99% identical to those of Taiwan, Thailand and Chinese isolates, respectively.