ABSTRACT
OBJECTIVE: The purpose of this study was to illustrate the role of NAA10 in aggravating the malignant progression of renal cell carcinoma (RCC) by upregulating UPK1B. PATIENTS AND METHODS: NAA10 levels in RCC tissues and paracancerous tissues were detected. Thereafter, the potential relationship between NAA10 level and clinical parameters of RCC patients was analyzed. After knockdown of NAA10, changes in proliferative potential of 786-O and Caki-1 cells were examined by cell counting kit-8 (CCK-8), colony formation and 5-Ethynyl-2'-deoxyuridine (EdU) assay. Finally, the regulatory role of NAA10 in the downstream gene UPK1B and the involvement of UPK1B in the development of RCC were determined via rescue experiments. RESULTS: NAA10 was upregulated in RCC tissues than paracancerous tissues. Tumor staging was much worse in RCC patients expressing a higher level of NAA10. Knockdown of NAA10 inhibited proliferative potential and downregulated UPK1B in RCC cells. Besides, NAA10 level was identified to be positively linked to UPK1B level in RCC tissues. At last, overexpression of UPK1B was able to abolish the inhibitory effect of silenced NAA10 on RCC proliferation. CONCLUSIONS: NAA10 level is closely linked to tumor staging and poor prognosis in RCC patients. NAA10 aggravates the malignant progression of RCC by upregulating UPK1B and may be a specific biomarker in RCC.
Subject(s)
Carcinoma, Renal Cell/metabolism , Kidney Neoplasms/metabolism , N-Terminal Acetyltransferase A/metabolism , N-Terminal Acetyltransferase E/metabolism , Uroplakin Ib/metabolism , Carcinoma, Renal Cell/pathology , Cell Proliferation , Cells, Cultured , Female , Humans , Kidney Neoplasms/pathology , Male , Middle Aged , N-Terminal Acetyltransferase A/genetics , N-Terminal Acetyltransferase E/genetics , Uroplakin Ib/geneticsABSTRACT
To study which subgroup of bone marrow derived cells formed myofibroblasts and the mechanism that transforming growth factor ß(1)(TGFß(1)) regulates the formation of bone marrow derived macrophages into myofibroblasts during renal fibrosis. Chimeric mice were generated by lethally irradiation of C57 mice followed by transfusion of green fluorescent protein (GFP) labeled bone marrow cells. Complete marrow reconstitution was developed until 12 weeks after transplantation. The mice were randomly divided into Sham operation group, unilateral ureteral obstruction (UUO) 3 days group, UUO5 days group, UUO7 days group and UUO7 with TGFß(1) treatment group. Each group had four mice. Flow cytometry was used to evaluate cell components. Compared with Sham operation group the proportions of GFP(+) CD(14)(+)α-smooth muscle actin(α-SMA)(+) cells, GFP+ CD(44)(+)CD(105)(+)α-SMA(+) cells and GFP(+) F4/80(+) α-SMA(+) cells in each UUO group were progressively increased and the transformation rate in UUO7 day group was the highest. The GFP(+) F4/80(+) α-SMA(+) cells accounted for the largest population. TGFß(1) promoted the transformation of bone marrow derived macrophages into myofibroblasts. Compared with Sham operation group or UUO7 day group, the proportion of GFP(+) F4/80(+) α-SMA(+) cells increased in UUO7 day TGFß(1) treatment group. Compared with Sham operation group (or UUO7 days group) the protein expressions of F4/80, α-SMA, Collagen â increased in UUO7 with TGFß(1) group. Bone marrow derived macrophages are considered as the main type of myofibroblast precursors during the development of renal fibrosis. TGFß(1) regulates the transformation of bone marrow-derived macrophages into myofibroblasts. This process contributes to progressive renal fibrosis and deterioration of renal function.
Subject(s)
Bone Marrow/pathology , Fibrosis/pathology , Kidney Diseases/pathology , Macrophages/pathology , Myofibroblasts/pathology , Transforming Growth Factor beta1/metabolism , Actins , Animals , Bone Marrow/metabolism , Bone Marrow Cells , Collagen Type I , Fibrosis/metabolism , Green Fluorescent Proteins , Kidney , Kidney Diseases/metabolism , Macrophages/metabolism , Mice , Myofibroblasts/metabolism , Transforming Growth Factor beta , Transforming Growth Factor beta1/geneticsABSTRACT
OBJECTIVE: To investigate the regulation effect of ß-catenin pathway on transforming growth factor beta1 (TGF-ß1) induced pulmonary pro-fibrosis. METHODS: The rat alveolar typeâ ¡ cells (RLE-6TN) were divided into four groups: A1.control group; B1.TGF-ß1 group was treated with 5 µg/L TGF-ß1; C1.pcDNA+ TGF-ß1 group was transiently transfected with eukaryotic expression vector pcDNA3.0 (pcDNA) and followed by TGF-ß1 treatment (5 µg/L); D1.F-(ß-TrCP)-Ecad+ TGF-ß1 group was transiently transfected with ß-catenin protein knockout vector [F-(ß-TrCP)-Ecad] and followed by TGF-ß1 treatment (5 µg/L). After 24 hours, cells were observed under the inverted phase contrast microscope, then the expressions of E-cadherin, α-smooth muscle actin (α-SMA) and fibronectin (Fn) in each group were measured by Western blot and the mRNA levels of Snail which was the downstream profibrotic transcription production in cell culture supernatants of each group were detected by real-time fluorescence quantification-polymerase chain reaction (RT-PCR) .The rat alveolar macrophages (CRL-2192) were divided into five groups: A2.control group; B2.Interferon gamma (IFN-γ) group was treated by 20 µg/L IFN-γ; C2.TGF-ß1+ IFN-γ group was treated by 20 µg/L IFN-γ with 10 µg/L TGF-ß1; D2.F-(ß-TrCP)-Ecad+ TGF-ß1+ IFN-γ group was transfected with F-(ß-TrCP)-Ecad and other dispose was the same as group C2; E2.WTß-catenin+ TGF-ß1+ IFN-γ group was transfected with WTß-catenin and other dispose was the same as group C2.After 24 hours, protein levels of ß-catenin in group A2, B2, C2 were determined by Western blot.Inducible nitric oxide synthase (iNOS) mRNA levels of each group were detected by RT-PCR. RESULTS: The RLE-6TN cells of group B1, C1 showed a change in morphology to spindle-shaped cells, the cells of group D1 maintained a cobblestone morphology. Protein expressions of the fibroblast markers α-SMA and Fn, and mRNA expressions of the downstream profibrotic transcription production Snail of group B1, C1 were significantly higher than group A1, while protein expressions of the epithelial marker E-cadherin were significantly lower.The protein expressions of α-SMA, Fn and mRNA expressions Snail of group D1 were significantly lower than group C1 (0.352±0.076 vs 0.937±0.303, 0.319±0.072 vs 0.903±0.211, 3.675±0.642 vs 9.708±2.031), while the protein expressions of E-cadherin were significantly higher (1.482±0.227 vs 0.604±0.121) (all P<0.05). The steady state protein levels of ß-catenin in CRL-2192 cells was low and ß-catenin protein expressions of CRL-2192 cells in group A2, B2 and C2 had no significantly statistical differences.The mRNA expressions of iNOS of group B2 cells were significantly higher than group A2, C2, D2, E2 (64.95±4.47 vs 9.87±0.73, 21.32±2.41, 18.35±3.61, 22.87±3.14) (all P<0.01), the expressions of iNOS of group C2, D2, E2 were all higher than group A2 (all P<0.05), but there were no significant differences among group C2, D2 and E2. CONCLUSIONS: Inhibition of ß-catenin pathway inhibits TGF-ß1-induced epithelial-mesenchymal transition (EMT) and has no effect on its anti-inflammation effect.Therefore, ß-catenin pathway regulates the pulmonary pro-fibrosis effect of TGF-ß1.
Subject(s)
Fibroblasts/metabolism , Transforming Growth Factor beta1/pharmacology , beta Catenin/metabolism , Actins , Animals , Antigens, CD , Cadherins , Epithelial-Mesenchymal Transition/drug effects , Epithelial-Mesenchymal Transition/genetics , Fibroblasts/cytology , Fibronectins , Interferon-gamma , Rats , Transforming Growth Factor beta1/metabolism , beta Catenin/geneticsABSTRACT
Based on first principles calculations and self-consistent solution of the linearized Boltzmann-Peierls equation for phonon transport approach within a three-phonon scattering framework, we characterize lattice thermal conductivities k of freestanding silicene, germanene and stanene under different isotropic tensile strains and temperatures. We find a strong size dependence of k for silicene with tensile strain, i.e., divergent k with increasing system size; however, the intrinsic room temperature k for unstrained silicene converges with system size to 19.34 W m(-1) K(-1) at 178 nm. The room temperature k of strained silicene becomes as large as that of bulk silicon at 84 µm, indicating the possibility of using strain in silicene to manipulate k for thermal management. The relative contribution to the intrinsic k from out-of-plane acoustic modes is largest for unstrained silicene, â¼39% at room temperature. The single mode relaxation time approximation, which works reasonably well for bulk silicon, fails to appropriately describe phonon thermal transport in silicene, germanene and stanene within the temperature range considered. For large samples of silicene, k increases with tensile strain, peaks at â¼7% strain and then decreases with further strain. In germanene and stanene, increasing strain hardens and stabilizes long wavelength out-of-plane acoustic phonons, and leads to similar k behaviors to those of silicene. These findings further our understanding of phonon dynamics in group-IV buckled monolayers and may guide transfer and fabrication techniques for these freestanding samples and engineering of k by size and strain for applications of thermal management and thermoelectricity.
ABSTRACT
In the field of metallic materials with amorphous structures, it is vitally important to understand the glass formation and to predict glass-forming ability (GFA) in terms of constituent elements and alloy compositions. In this study, an expression has been formulated from first-principles calculations to predict the trend of GFA by hybridizing both internal energies and atomic-scale defect structures. The prediction of GFA from compositions has been verified successfully by available experimental data in the model Zr-Cu alloy system. The physical scenario revealed here has extensive implications for the design of bulk metallic glasses with superior GFA.
ABSTRACT
Spin-polarized density functional theory is employed to investigate the mechanical and magnetic properties of a (5, 5) carbon nanotube (CN) with a mono-vacancy. It is found that the magnetic properties of a defective CN can be modified by applied uniaxial tensile strain. The effects of uniaxial strains on the magnetic properties are related to the stretched bonds in the defective CN, and the effect of a mixture of sp(2) and sp(3) hybridization on the magnetism is investigated. Furthermore, because of the strong magneto-mechanical coupling between the defective CN and metal, the mechanical properties of the defective (5, 5) CN are found to be significantly alternated by the substitution of metal atoms to its vacancy sites. Such strong coupling among magnetic moment, spin-dependent transport, and mechanical deformation in a defective CN could be beneficial in some potential applications of CNs in spintronic devices and metal matrix composites.
ABSTRACT
Programmed death 1 (PD-1) is a novel member of the CD28/cytotoxic T-lymphocyte-associated protein-4 superfamily, which plays an important role in the regulation of activated T cells. However, it is not clear how PD-1 is expressed in normal and diseased kidney, nor if it has a role in progression of chronic renal disease. PD-1 expression and the effect of monoclonal anti-PD-1 antibody (Ab) were examined in murine adriamycin nephropathy (AN). BALB/c mice were divided into three groups: (a) normal mice, (b) adriamycin (ADR) with control immunoglobulin (Ig)G (ADR-IgG), and (c) ADR with anti-PD-1 Ab (ADR-Ab). AN was induced by a single intravenous injection of ADR. Anti-PD-1 Ab was given by intraperitoneal injection on alternate days from day 0 to day 10, or to day 18. Animals were killed at week 4. Renal function, histological change, and cytokine expression were examined. PD-1 mRNA was detected in kidney tissue of mice with AN in a dose- and time-dependent manner. PD-1 was mainly expressed on injured tubule cells and some interstitial cells, which co-stained with alpha-smooth muscle actin in AN, but not in normal kidney. Anti-PD-1 treatment up to day 18, but not to day 10, worsened glomerular and tubulointerstitial injury. The ratio of urinary protein/creatinine was significantly higher in ADR-Ab mice than ADR-IgG mice. The number of macrophages was significantly increased in ADR-Ab mice compared with ADR-IgG mice. Blockade of PD-1 worsened progressive renal histopathological and functional injury in murine AN. This suggests a possible protective role for PD-1 in chronic renal disease, and its potential as a treatment to slow disease progression.
Subject(s)
B7-1 Antigen/immunology , Doxorubicin , Glomerulosclerosis, Focal Segmental/pathology , Kidney Failure, Chronic/pathology , Membrane Glycoproteins/immunology , Peptides/immunology , Actins/immunology , Animals , Antibodies, Monoclonal/immunology , B7-1 Antigen/administration & dosage , B7-1 Antigen/genetics , B7-1 Antigen/physiology , B7-H1 Antigen , Creatinine/urine , Cricetinae , Data Interpretation, Statistical , Disease Models, Animal , Disease Progression , Dose-Response Relationship, Drug , Doxorubicin/administration & dosage , Enzyme-Linked Immunosorbent Assay , Fluorescent Antibody Technique , Glomerulosclerosis, Focal Segmental/chemically induced , Glomerulosclerosis, Focal Segmental/genetics , Glomerulosclerosis, Focal Segmental/immunology , Glomerulosclerosis, Focal Segmental/metabolism , Glomerulosclerosis, Focal Segmental/therapy , Immunoglobulin G/immunology , Immunoglobulins/immunology , Immunohistochemistry , Injections, Intraperitoneal , Injections, Intravenous , Kidney Failure, Chronic/chemically induced , Kidney Failure, Chronic/genetics , Kidney Failure, Chronic/immunology , Kidney Failure, Chronic/metabolism , Kidney Failure, Chronic/therapy , Kidney Glomerulus/pathology , Kidney Tubules/pathology , Macrophages , Membrane Glycoproteins/administration & dosage , Membrane Glycoproteins/genetics , Membrane Glycoproteins/physiology , Mice , Mice, Inbred C57BL , Peptides/administration & dosage , Peptides/genetics , Peptides/physiology , Proteinuria/diagnosis , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction , Staining and Labeling/methods , Time FactorsABSTRACT
Molecular dynamics simulations are carried out to study the incipient dislocation plasticity in Ni3Al. Dislocation nucleation is found to occur preferentially at energetic atomic clusters with larger-than-average relative displacements. From the simulated distribution of the atomic relative displacements, a scaling model is proposed to predict the size dependence of the incipient plasticity condition in real-sized specimens.
ABSTRACT
Dynamic scaling for fracture or breakdown process in disordered systems is investigated in a two-dimensional random field Ising model (RFIM). We find two evolving stages in the avalanche process in the RFIM. At the short-time regime, a power-law growth of the avalanche size Deltas is observed; and at late times, the conventional nucleation and growth process is found. At the critical point of the RFIM, the avalanche size is found to obey the dynamic scaling law Delta(s) approximately equal t((d-beta/nu)/z). From this dynamic scaling relation, the critical strength of the random field D(c) and the critical exponents, beta, nu, and z, are determined. The observed dynamics is explained by a simple nucleation theory of first-order phase transformations.