scholarly journals Identification of Membrane-Bound Lytic Murein Transglycosylase A (MltA) as a Growth Factor for Francisella novicida in a Silkworm Infection Model

2021 ◽  
Vol 10 ◽  
Author(s):  
Takemasa Nakamura ◽  
Takashi Shimizu ◽  
Fumiya Inagaki ◽  
Shoma Okazaki ◽  
Shib Shankar Saha ◽  
...  
Keyword(s):  
Growth Factor ◽  
Human Monocyte ◽  
Infection Model ◽  
Intracellular Growth ◽  
Ovary Cells ◽  
Growth And Survival ◽  
Francisella Novicida ◽  
Transposon Mutants ◽  
Membrane Bound ◽  
Number Of Bacteria

Francisella tularensis, the causative agent of tularemia, is transmitted by arthropod vectors within mammalian hosts. The detailed mechanisms contributing to growth and survival of Francisella within arthropod remain poorly understood. To identify novel factors supporting growth and survival of Francisella within arthropods, a transposon mutant library of F. tularensis subsp. novicida (F. novicida) was screened using an F. novicida–silkworm infection model. Among 750 transposon mutants screened, the mltA-encoding membrane-bound lytic murein transglycosylase A (MltA) was identified as a novel growth factor of F. novicida in silkworms. Silkworms infection with an mltA deletion mutant (ΔmltA) resulted in a reduction in the number of bacteria and prolonged survival. The ΔmltA strain exhibited limited intracellular growth and cytotoxicity in BmN4 silkworm ovary cells. Moreover, the ΔmltA strain induced higher expression of the antimicrobial peptide in silkworms compared to the wild-type strain. These results suggest that F. novicida MltA contributes to the survival of F. novicida in silkworms via immune suppression-related mechanisms. Intracellular growth of the ΔmltA strain was also reduced in human monocyte THP-1 cells. These results also suggest the contribution of MltA to pathogenicity in humans and utility of the F. novicida–silkworm infection model to explore Francisella infection.

Insulin-Like Growth Factor-I and Transferrin Mediate Growth and Survival of Chinese Hamster Ovary Cells

2000 ◽  
Vol 16 (5) ◽  
pp. 698-702 ◽  
Author(s):  
N.-A.S. Sunstrom ◽  
R.D. Gay ◽  
D.C. Wong ◽  
N.A. Kitchen ◽  
L. DeBoer ◽  
...  
Keyword(s):  
Growth Factor ◽  
Chinese Hamster Ovary ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Insulin Like Growth Factor ◽  
Ovary Cells ◽  
Growth And Survival ◽  
Factor I ◽  
Growth Factor I

scholarly journals Interactions between Rainbow Trout Eyed Eggs and Flavobacterium spp. Using a Bath Challenge Model: Preliminary Evaluation of Bacteriophages as Pathogen Control Agents

2021 ◽  
Vol 9 (5) ◽  
pp. 971
Author(s):  
Valentina L. Donati ◽  
Inger Dalsgaard ◽  
Anniina Runtuvuori-Salmela ◽  
Heidi Kunttu ◽  
Johanna Jørgensen ◽  
...  
Keyword(s):  
Rainbow Trout ◽  
Pathogenic Bacteria ◽  
Infection Model ◽  
Preliminary Evaluation ◽  
Fish Eggs ◽  
Short Term ◽  
Rainbow Trout Oncorhynchus Mykiss ◽  
Pathogen Control ◽  
Number Of Bacteria ◽  
Bath Challenge

The microbial community surrounding fish eyed eggs can harbor pathogenic bacteria. In this study we focused on rainbow trout (Oncorhynchus mykiss) eyed eggs and the potential of bacteriophages against the pathogenic bacteria Flavobacterium psychrophilum and F. columnare. An infection bath method was first established, and the effects of singular phages on fish eggs was assessed (survival of eyed eggs, interaction of phages with eyed eggs). Subsequently, bacteria-challenged eyed eggs were exposed to phages to evaluate their effects in controlling the bacterial population. Culture-based methods were used to enumerate the number of bacteria and/or phages associated with eyed eggs and in the surrounding environment. The results of the study showed that, with our infection model, it was possible to re-isolate F. psychrophilum associated with eyed eggs after the infection procedure, without affecting the survival of the eggs in the short term. However, this was not possible for F. columnare, as this bacterium grows at higher temperatures than the ones recommended for incubation of rainbow trout eyed eggs. Bacteriophages do not appear to negatively affect the survival of rainbow trout eyed eggs and they do not seem to strongly adhere to the surface of eyed eggs either. Finally, the results demonstrated a strong potential for short term (24 h) phage control of F. psychrophilum. However, further studies are needed to explore if phage control can be maintained for a longer period and to further elucidate the mechanisms of interactions between Flavobacteria and their phages in association with fish eggs.

scholarly journals Recombinant type 1 transforming growth factor beta precursor produced in Chinese hamster ovary cells is glycosylated and phosphorylated.

1988 ◽  
Vol 8 (5) ◽  
pp. 2229-2232 ◽  
Author(s):  
A M Brunner ◽  
L E Gentry ◽  
J A Cooper ◽  
A F Purchio
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Chinese Hamster Ovary ◽  
Transforming Growth Factor ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Tgf Beta ◽  
Ovary Cells ◽  
Growth Factor Beta

Analyses of cDNA clones coding for simian type 1 transforming growth factor beta (TGF-beta 1) suggest that there are three potential sites for N-linked glycosylation located in the amino terminus of the precursor region. Analysis of [3H]glucosamine-labeled serum-free supernatants from a line of Chinese hamster ovary cells which secrete high levels of recombinant TGF-beta 1 indicate that the TGF-beta 1 precursor, but not the mature form, is glycosylated. Digestion with neuraminidase resulted in a shift in migration of the two TGF-beta 1 precursor bands, which suggests that they contain sialic acid residues. Endoglycosidase H had no noticeable effect. Treatment with N-glycanase produced two faster-migrating sharp bands, the largest of which had a molecular weight of 39 kilodaltons. TGF-beta 1-specific transcripts produced by SP6 polymerase programmed the synthesis of a 42-kilodalton polypeptide which, we suggest, is the unmodified protein backbone of the precursor. Labeling with 32Pi showed that the TGF-beta 1 precursor was phosphorylated in the amino portion of the molecule.

scholarly journals Isoprocurcumenol Supports Keratinocyte Growth and Survival through Epidermal Growth Factor Receptor Activation

2021 ◽  
Vol 22 (22) ◽  
pp. 12579
Author(s):  
Paul Kwangho Kwon ◽  
Sung Wook Kim ◽  
Ranjit De ◽  
Sung Woo Jeong ◽  
Kyong-Tai Kim
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Receptor Activation ◽  
Cellular Damage ◽  
Major Type ◽  
Growth And Survival ◽  
Biosensor System ◽  
Key Factor ◽  
Epidermal Growth

Although proliferation of keratinocytes, a major type of skin cells, is a key factor in maintaining the function of skin, their ability to proliferate tends to diminish with age. To solve such a problem, researchers in medical and skin cosmetic fields have tried to utilize epidermal growth factor (EGF), but achieved limited success. Therefore, a small natural compound that can mimic the activity of EGF is highly desired in both medical and cosmetic fields. Here, using the modified biosensor system, we observed that natural small-compound isoprocurcumenol, which is a terpenoid molecule derived from turmeric, can activate EGFR signaling. It increased the phosphorylation of ERK and AKT, and upregulated the expression of genes related to cell growth and proliferation, such as c-myc, c-jun, c-fos, and egr-1. In addition, isoprocurcumenol induced the proliferation of keratinocytes in both physical and UVB-induced cellular damage, indicative of its function in skin regeneration. These findings reveal that EGF-like isoprocurcumenol promotes the proliferation of keratinocytes and further suggest its potential as an ingredient for medical and cosmetics use.

scholarly journals Endogenous growth factor stimulation of hemocyte proliferation induces resistance to Schistosoma mansoni challenge in the snail host

2016 ◽  
Vol 113 (19) ◽  
pp. 5305-5310 ◽  
Author(s):  
Emmanuel A. Pila ◽  
Michelle A. Gordy ◽  
Valerie K. Phillips ◽  
Alethe L. Kabore ◽  
Sydney P. Rudko ◽  
...  
Keyword(s):  
Growth Factor ◽  
Schistosoma Mansoni ◽  
Endogenous Growth ◽  
Immune Cells ◽  
Functional Characterization ◽  
Immunological Response ◽  
Snail Host ◽  
Infection Model ◽  
Proliferation And Differentiation ◽  
Exogenous Factors

Digenean trematodes are a large, complex group of parasitic flatworms that infect an incredible diversity of organisms, including humans. Larval development of most digeneans takes place within a snail (Gastropoda). Compatibility between snails and digeneans is often very specific, such that suitable snail hosts define the geographical ranges of diseases caused by these worms. The immune cells (hemocytes) of a snail are sentinels that act as a crucial barrier to infection by larval digeneans. Hemocytes coordinate a robust and specific immunological response, participating directly in parasite killing by encapsulating and clearing the infection. Hemocyte proliferation and differentiation are influenced by unknown digenean-specific exogenous factors. However, we know nothing about the endogenous control of hemocyte development in any gastropod model. Here, we identify and functionally characterize a progranulin [Biomphalaria glabrata granulin (BgGRN)] from the snail B. glabrata, a natural host for the human blood fluke Schistosoma mansoni. Granulins are growth factors that drive proliferation of immune cells in organisms, spanning the animal kingdom. We demonstrate that BgGRN induces proliferation of B. glabrata hemocytes, and specifically drives the production of an adherent hemocyte subset that participates centrally in the anti-digenean defense response. Additionally, we demonstrate that susceptible B. glabrata snails can be made resistant to infection with S. mansoni by first inducing hemocyte proliferation with BgGRN. This marks the functional characterization of an endogenous growth factor of a gastropod mollusc, and provides direct evidence of gain of resistance in a snail-digenean infection model using a defined factor to induce snail resistance to infection.

scholarly journals The role of renal dipeptidyl peptidase-4 in kidney disease: renal effects of dipeptidyl peptidase-4 inhibitors with a focus on linagliptin

2018 ◽  
Vol 132 (4) ◽  
pp. 489-507 ◽  
Author(s):  
Keizo Kanasaki
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Growth Factor ◽  
Kidney Disease ◽  
Dipeptidyl Peptidase ◽  
Renal Effects ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Membrane Bound

Emerging evidence suggests that dipeptidyl peptidase-4 (DPP-4) inhibitors used to treat type 2 diabetes may have nephroprotective effects beyond the reduced renal risk conferred by glycemic control. DPP-4 is a ubiquitous protein with exopeptidase activity that exists in cell membrane-bound and soluble forms. The kidneys contain the highest levels of DPP-4, which is increased in diabetic nephropathy. DPP-4 inhibitors are a chemically heterogeneous class of drugs with important pharmacological differences. Of the globally marketed DPP-4 inhibitors, linagliptin is of particular interest for diabetic nephropathy as it is the only compound that is not predominantly excreted in the urine. Linagliptin is also the most potent DPP-4 inhibitor, has the highest affinity for this protein, and has the largest volume of distribution; these properties allow linagliptin to penetrate kidney tissue and tightly bind resident DPP-4. In animal models of kidney disease, linagliptin elicited multiple renoprotective effects, including reducing albuminuria, glomerulosclerosis, and tubulointerstitial fibrosis, independent of changes in glucagon-like peptide-1 (GLP-1) and glucose levels. At the molecular level, linagliptin prevented the pro-fibrotic endothelial-to-mesenchymal transition by disrupting the interaction between membrane-bound DPP-4 and integrin β1 that enhances signaling by transforming growth factor-β1 and vascular endothelial growth factor receptor-1. Linagliptin also increased stromal cell derived factor-1 levels, ameliorated endothelial dysfunction, and displayed unique antioxidant effects. Although the nephroprotective effects of linagliptin are yet to be translated to the clinical setting, the ongoing Cardiovascular and Renal Microvascular Outcome Study with Linagliptin in Patients with Type 2 Diabetes Mellitus (CARMELINA®) study will definitively assess the renal effects of this DPP-4 inhibitor. CARMELINA® is the only clinical trial of a DPP-4 inhibitor powered to evaluate kidney outcomes.

Synthesis of membrane-bound colony-stimulating factor 1 (CSF-1) and downmodulation of CSF-1 receptors in NIH 3T3 cells transformed by cotransfection of the human CSF-1 and c-fms (CSF-1 receptor) genes

1987 ◽  
Vol 7 (7) ◽  
pp. 2378-2387 ◽  
Author(s):  
C W Rettenmier ◽  
M F Roussel ◽  
R A Ashmun ◽  
P Ralph ◽  
K Price ◽  
...  
Keyword(s):  
Growth Factor ◽  
Disulfide Bonds ◽  
Mononuclear Phagocyte ◽  
Transformed Cells ◽  
Colony Stimulating Factor ◽  
3T3 Cells ◽  
Membrane Bound ◽  
Nih 3T3 ◽  
Stimulating Factor ◽  
Nih 3T3 Cells

NIH 3T3 cells cotransfected with the human c-fms proto-oncogene together with a 1.6-kilobase cDNA clone encoding a 256-amino-acid precursor of the human mononuclear phagocyte colony-stimulating factor CSF-1 (M-CSF) undergo transformation by an autocrine mechanism. The number of CSF-1 receptors on the surface of transformed cells was regulated by ligand-induced receptor degradation and was inversely proportional to the quantity of CSF-1 produced. A tyrosine-to-phenylalanine mutation at position 969 near the receptor carboxyl terminus potentiated its transforming efficiency in cells cotransfected by the CSF-1 gene but did not affect receptor downmodulation. CSF-1 was synthesized as an integral transmembrane glycoprotein that was rapidly dimerized through disulfide bonds. The homodimer was externalized at the cell surface, where it underwent proteolysis to yield the soluble growth factor. Trypsin treatment of viable cells cleaved the plasma membrane form of CSF-1 to molecules of a size indistinguishable from that of the extracellular growth factor, suggesting that trypsinlike proteases regulate the rate of CSF-1 release from transformed cells. The data raise the possibility that this form of membrane-bound CSF-1 might stimulate receptors on adjacent cells through direct cell-cell interactions.

Sign in / Sign up

Export Citation Format

Share Document