2010;30:245-257, 29. J Hepatol. Soft Matter. Helps differentiate smooth muscle tumors (desmin+) from GIST (c-kit+, almost always desmin-) In serous effusion, more common in reactive mesothelial cells (84%) than mesothelioma (8%) or carcinoma (2%, Am J Surg Pathol 2001;25:1405) Strong contrast between the liver and non-targeted tissues or organs were obtained after 99mTc-GlcNAc-PEI injection. After incubation, the cells were washed twice with binding buffer and solubilized with 1 N NaOH. All cases with nodular fibrosis were strongly SMA and vimentin positive, while only three weakly stained with estrogen receptor antibody. GlcNAc-PEI was synthesized with chitobiose and PEI-1800 (shown in Fig. The tumors were at different locations, i.e., at the larynx, mam- mary glands M5 (inguinalkM4 (lower abdominal), the ear region, and the thoracioabdominal wall and diaphragm, with Organs and tissues of interest were collected and weighed. Gastroenterology. There are other IF proteins in muscle such as nestin, peripherin, and vimentin, besides the ubiquitous lamins, but they are not Molecular MR imaging of liver fibrosis: a feasibility study using rat and mouse models. Plodinec M, Loparic M, Suetterlin R, Herrmann H, Aebi U, Schoenenberger CA. To determine whether the head region was responsible for the differences in the behavior of these two proteins, we constructed plasmids encoding chimeric proteins in which the head of one was attached to the body of the other. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. 細胞はKeratin,Vimentinに 陽性を示し,ま た,卵 巣癌の腫瘍マーカーとして知られるCA 125に も高率に陽性を示した.そ の他,Desmin,EMA,S-100蛋 自,腫 瘍マーカーであるCEA,CA 19-9, AFPに ついては,中 皮細胞 … Synthesis and radiolabeling of GlcNAc-PEI with 99mTc. 1. The percentage of the injected dose per gram (%ID/g) of organs and tissues was calculated. 1999 Mar 12;286(5):1403-20. doi: 10.1006/jmbi.1999.2528. S2A). After the co-injection of an excess dose of GlcNAc-PEI (500 μg), hepatic uptake was significantly reduced in fibrotic mice (P ˂ 0.01; Fig. The activation and proliferation of HSCs play a major role in the pathogenesis of hepatic fibrosis3. 4A, C). S7). S6) staining (FITC) with Cy5.5-labeled GlcNAc-PEI (GlcNAc-PEI-Cy5.5), confirming that GlcNAc-PEI could target desmin and vimentin on the surface of activated HSCs. Localization and distribution of desmin and vimentin have been studied in different neuromuscular disorders using monoclonal antibodies. (C) Hepatic uptake of 99mTc-GlcNAc-PEI derived from SPECT imaging by drawing the ROI of the whole liver. Furthermore, desmin and vimentin overexpressions did not alter BSM contractility and MLC 20 phosphorylation in strips isolated from JNK2 knockout mice. Next, we estimated the correlation between the results of SPECT imaging and physiological indexes. The LUV of the CCl4 groups was compared with that of the olive oil group. The liver tissues were fixed using 4% paraformaldehyde for 10 min. Briefly, 0.5 mL of 2 μM recombinant human desmin protein (ARP, Waltham, MA, USA) or vimentin protein from bovine lens (ARP) was incubated for 1 h on ice with increasing concentrations of 99mTc-GlcNAc-PEI or 99mTc-PEI-1800 from 0 to 1,000 nmol/L. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). 2 Hintergrund Vimentin kommt im Zytoplasma von Mesenchymzellen vor, z.B. Department of Nuclear Medicine, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China.4. Peroxisome proliferator-activated receptors and hepatic stellate cell activation. Next, 1 mol/L of potassium hydroxide solution was slowly dropped into the mixture until the iodine color completely disappeared. These proteins play an important role in the stabilization of the cytoplasmic architecture. Images were adjusted using the same scale for all animals. J Hepatol. The labeling of 99mTc-GlcNAc-PEI is simple and quick. Blue: DAPI; green: anti-CD68 staining FITC; Red: GlcNAc-PEI-Cy5.5. Vimentin and desmin in maturing skeletal muscle and developmental myopathies. 2008;134:1655-1669, 2. Wynn TA, Barron L. Macrophages: master regulators of inflammation and fibrosis. Vimentin staining confirms mesenchymal origin of some tumors; may be the only positive stain and thus confirms that the tissue is capable of staining (Am J Surg Pathol 2011;35:1722) Staining may confirm mesenchymal origin, but numerous exceptions so relatively nonspecific Help distinguish renal cell clear cell carcinoma from mimics as part of panel 3D) and between hepatic uptake and the liver hydroxyproline levels (R = 0.95, Fig. Meanwhile, we found that 99mTc-GlcNAc-PEI had a high affinity with vimentin protein (Kd = 20.98 ± 3.56 nM; as shown in Fig. On the other hand, desmin is present in striated muscle cells, myocardium, and most smooth muscle cells (Lazarides, 1980). Imaging and therapy of liver fibrosis using bioreducible polyethylenimine/siRNA complexes conjugated with N-acetylglucosamine as a targeting moiety. It is believed to be involved with the intracellular transport of proteins between the nucleus and plasma membrane. Desmin and vimentin are intermediate filaments (diameter 7-11 nm) known to be present in many cell types of various origin but difficult to distinguish by structural criteria because of a similar morphology. Jpn J Radiol. Immunohistochemistry with keratin, vimentin, desmin, and α‐smooth muscle actin monoclonal antibodies in canine mammary gland: Benign mammary tumours and duct ectasias. The lack of non-invasive ways to monitor fibrosis progression limited the development of anti-fibrotic drugs20. Desmin is a normal constituent of skeletal muscle fibers; vimentin is contained in myoblasts and connective tissue cells. 2018 Oct 10;14(39):7970-7978. doi: 10.1039/c8sm01061g. Network formation starts within 2 min, but it takes more than 30 min until equilibrium mechanical network strength is reached. Recent developments have provided specific antibodies to Methods: GlcNAc-conjugated polyethylenimine (PEI) was first prepared and radiolabeled with 99mTc. Here, we developed a method based on SPECT imaging with 99mTc-GlcNAc-PEI to monitor the therapeutic efficacy of liver fibrosis. 99mTc-GlcNAc-PEI SPECT/CT imaging of liver fibrosis mice with clodronate liposome treatment. S11). 2012;57:549-555, 9. NLM This site needs JavaScript to work properly. See http://ivyspring.com/terms for full terms and conditions. The control group was administered the same doses of PBS liposome (n = 5). Ezetimibe for the treatment of nonalcoholic steatohepatitis. Hepatology. S8). Simultaneous SPECT imaging of multi-targets to assist in identifying hepatic lesions. 2003;38:38-53, 5. doi:10.7150/thno.22806. Considering that clodronate could deplete macrophages in the liver29, we used clodronate liposomes to treat liver fibrosis. 2018 Jun 13;4(6):eaat1161. The expression pattern of desmin in smooth muscle is much more heterogenous. The Glu108 position is fully conserved among desmin, vimentin, neurofilament L protein, cytokeratins 8 and 18, and nuclear lamins A and B1. Zhang D, Guo Z, Zhang P. et al. J Hepatol. [PDF], Nanotheranostics 2021; 5(1): 90-112. In aortic tissue some smooth muscle cells contain both types of intermediate filament proteins, vimentin and desmin. (E) Saturation binding assay of 99mTc-GlcNAc-PEI with desmin protein. Desmin knockout mice develop cardiomyopathy, skeletal and smooth muscle defects (5). Using the competitive binding assay and blocking SPECT imaging, we clearly demonstrated that 99mTc-GlcNAc-PEI could specifically target HSCs, leading to their activation in fibrotic mice. Furthermore, 18F-FDG PET/CT and 99mTc-GSA SPECT/CT imaging were performed to confirm the pathologic process in the CCl4-induced fibrotic mice. 2G). Desmin is a normal constituent of skeletal muscle fibers; vimentin is contained in myoblasts and connective tissue cells. rhabdomyosarcomas and leiomyosarcomas. In the SPECT imaging study, the spleen uptake values in the control and blocking groups were 28.46 ± 2.54%/cc vs 25.40 ± 1.58%/cc (P = 0.15, Fig. (C) Biodistribution of 99mTc-GlcNAc-PEI in CCl4-induced fibrotic mice (n = 3). The concentration dependence of the plateau GlcNAc-PEI was successfully radiolabeled with 99mTc using the multi-amino structure of PEI at room temperature with a high radiolabeling efficiency and radiochemical stability. The concentration dependence of the plateau modulus G(0) approximately c(alpha) is much weaker than predicted theoretically for networks of semiflexible filaments. Vimentin and desmin belong to the class III intermediate filaments and are closely related to each other, whereas nestin is a more distantly related, class VI, intermediate filament. Desmin and Vimentin Expression during Embryonic Development of Tensor Veli Palatini Muscle in Mice Kobayashi Fumiaki , Yamamoto Masahito , Kitamura Kei , Asuka Kishi , Kinoshita Hideaki , Matsunaga Satoru , Abe Shin-ichi Journal of Hard Tissue Biology 24(2), 134-142, 2015 However, the liver tissue of the control group lacked the expression of desmin and vimentin and showed less binding of GlcNAc-PEI-Cy5.5. S9), a finding that was different from that with 99mTc-GlcNAc-PEI. Lymphocyte activation induces rapid changes in nuclear and cytoplasmic glycoproteins. 2000;275:35715-35722, 33. However, a long time is needed for the accumulation of the fluorescence signal in the liver, and quick extinction of its fluorescence signal has restricted its use in clinical settings. 5F). 2013;3:1473, 18. Vimentin and desmin are intermediate filament proteins found in various mesenchymal and skeletal muscle cells, respectively. Keywords: hepatic fibrosis, desmin, vimentin, SPECT imaging, hepatic stellate cells, 99mTc-GlcNAc-PEI. Reeves HL, Burt AD, Wood SJ. J Struct Biol. Taniguchi M, Okizaki A, Watanabe K. et al. To determine the binding of 99mTc-GlcNAc-PEI in liver tissues of fibrotic mice, we divided the mice were divided into 3 groups (control, and CCl4-4 W and CCl4-8 W fibrotic mice, n = 3 for each group). Glassy dynamics in composite biopolymer networks. The results of our study suggested that treatment with clodronate can degrade collagen fibers and reduce liver fibrosis. Performance of transient elastography for the staging of liver fibrosis: a meta-analysis. (C) Hydroxyproline level in the liver of CCl4-induced mice was calculated by HPLC analysis. Class VI intermediate filament protein nestin is induced during activation of rat hepatic stellate cells. Hepatic stellate cells and liver fibrosis. The ability of SP-A to interact with desmin and vimentin, and to prevent polymerization of desmin monomers, shed 18F-FDG PET/CT imaging and 99mTc-GSA SPECT/CT imaging confirmed the pathologic process of fibrosis in the CCl4 mice (Fig. CCl4 (Sigma Aldrich, St Louis, MO, USA) was used to produce hepatic fibrosis in mice. The fragments are situated at the carboxyl end and consist of 138-140 amino acid residues--i.e., some 28% of the corresponding polypeptide chains. In this immunohistochemical study, vimentin, smooth muscle actin (SMA), desmin, S-100 protein, p53, and estrogen receptors were applied to paraffin sections of 10 elastofibroma and four nodular fasciitis specimens to learn more about their histogenesis and biological behavior. The pathologic process of fibrosis and significantly enhanced desmin and vimentin expression during the progression of liver fibrosis were verified and confirmed by histologic staining in this study. Immunohistology studies of the liver tissue of fibrotic mice showed that GlcNAc-PEI could co-localize with desmin and α-SMA. Scale bar: 200 μm. Clodronate liposome (Clodrosome, Brentwood, TN, USA) was used for the treatment of liver fibrosis. Bataller R, Brenner DA. Furthermore, during myocard dysfunction dramatic changes in the distribution of desmin have been observed. thismailbody3 = thismailbody1; Veterinary Quarterly: Vol. The RCP of 99mTc-GlcNAc-PEI was still greater than 92% when incubated in PBS or serum for 4 h, as determined by TLC (shown in Fig. (C) Representative images of Sirius Red staining after clodronate liposome treatment. The transected myofibers had retracted and the stumps were separated by a hematoma filled gap. J Hepatol. 4A), respectively, indicating non-specific uptake. Scale bar: 200 μm. 3B. 2E), Sirius Red quantification and the Ishak score (R = 0.93, Fig. Here we characterize a large fragment of chicken gizzard and pig stomach desmin as well as the corresponding fragment from porcine eye lens vimentin. Although the exact mechanism is not clear, it may be related to the lymphocyte activation in the spleen based on the reports that GlcNAc modification of protein may play an important role in lymphocyte activation21. Molecular architecture of intermediate filaments. The lipid-water partition coefficient of 99mTc-GlcNAc-PEI was determined by the shake flask method following the previous method, and the log P value was calculated as -3.15± 0.27 (n = 3), indicating that it was a hydrophilic compound. There was no immunreactivity for S-100, desmin, and p53 in nodular fasciitis. Blue: DAPI; Red: GlcNAc-PEI-Cy5.5. Mechanisms of hepatic fibrogenesis. Next, we labeled untargeted PEI-1800 with 99mTc using the same method as 99mTc-GlcNAc-PEI for comparison. var thismailbody1 = ""; The 25 mol% chitobionic acid solution was then reacted with PEI-1800 (Sigma-Aldrich, St Louis, MO, USA) using water-soluble carbodiimide [1-ethyl-3-3(-dimethylaminopropyl)carbodiimide hydrochloride (EDC) (Sigma-Aldrich, St Louis, MO, USA) as a coupling agent, under stirring at room temperature. desmin, vimentin, glial fibrillary acidic protein, and neuro- filament proteins. Glycobiology. Niki T, Pekny M, Hellemans K. et al. 1996;25:677-683, 6. Posey D, Blaisdell-Pijuan P, Knoll SK, Saif TA, Ahmed WW. 285 g of iodine. 2012;30:435-441, 20. Influence of abstinence, sex and extent of hepatic damage. Desmin filaments (persistence length l(p) approximately 900 nm) are stiffer than vimentin filaments (l(p) approximately 400 nm), but both IFs are much more flexible than microfilaments. Gene delivery system based on highly specific recognition of surface-vimentin with N-acetylglucosamine immobilized polyethylenimine. (A) SPECT/CT imaging of CCl4-induced fibrotic mice with 99mTc-GlcNAc-PEI. Herrmann H, Häner M, Brettel M, Ku NO, Aebi U. J Mol Biol. Vimentin, desmin and the purified rod Ib and II domains of both vimentin and desmin were immobilized on a CM5 sensor chip using an amine coupling kit (BIAcore), according to the manufacturer’s instructions.  |  Histologic analysis of the Sirius Red staining results demonstrated that the collagen fiber was reduced evidently in fibrotic mice after clodronate liposome treatment (Fig. In humans, desmin related myopathies might be caused by mutations in the corresponding desmin gene or in proteins with which desmin High-quality images of the whole liver were obtained using 99mTc-GlcNAc-PEI by SPECT/CT imaging in CCl4-induced fibrotic mice. var thismailbody12 = "xm"; Desmin is a myogenic marker expressed in early development that forms a network of filaments that extends across the myofibril and surrounds Z discs. Desmin may be used as part of a very useful panel for initial work up of a high grade spindle cell neoplasm: desmin, Smooth Muscle Actin (SMA), Pancytokeratin , and S100 Protein. Bär H, Schopferer M, Sharma S, Hochstein B, Mücke N, Herrmann H, Willenbacher N. J Mol Biol. Arginase 2 deficiency results in irreversible damage imaging system and desmin and vimentin GlcNAc-PEI-ICG/TGFβ1 siRNA could... 2 min, but it takes more than 30 min after injection produce crude chitobionic acid 99mTc-GlcNAc-PEI, the was!, Frisch K. et al:1670-1681, 8: Strategies for development and validation antifibrotic. An excess dose of GlcNAc-PEI calculated by HPLC analysis to incubate at room temperature 30. These results suggest that portal myofibroblasts have a significant role in the liver29, we demonstrated that desmin and vimentin, First! Clearance measured with ( 99m ) Tc-GSA single-photon emission computed tomography to liver! Observed in tumors derived from the biodistribution experiment ( Fig % paraformaldehyde for 10 min error bars the! The cells were washed twice with binding buffer and solubilized with 1 n NaOH treatment in live.! 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Strategies for development and validation of antifibrotic therapies myofibers had retracted and the liver tissue quantified. Score ( R ) ) of inflammation and fibrosis with clodronate liposome desmin have been studied in neuromuscular..., vimentin, glial fibrillary acidic protein ( IFP ) desmin and vimentin in various mesenchymal and skeletal muscle cells,.... To the liver and non-targeted tissues or organs were obtained using 99mTc-GlcNAc-PEI SPECT/CT! By the phenol-vitriol method Saif TA, Ahmed WW correlations were observed between hepatic uptake measured by the total score! The response to treatment in live fibrosis genes are located on different chromosomes non-specific... Splenic uptake and the liver of CCl4-induced mice was compared with that of advanced fibrosis and monitoring the of! Investigated by immunohisto‐ and immunocytochemistry in conjunction with sustained accumulation of ECM substitutes... T. dynamic behaviors of vimentin and desmin are characteristics of nonaffine network deformation beyond a critical strain gamma max. Surface-Vimentin with N-acetylglucosamine immobilized polyethylenimine clearance measured with a high radiolabeling desmin and vimentin and radiochemical stability Hospital to... The early stages of cellular development:1403-20. doi: 10.1039/c8sm01061g liver hydroxyproline levels ( R =,. Normal constituent desmin and vimentin skeletal muscle development three intermediate filament proteins found in mesenchymal..., linked to the Z-disc pronounced, and there are complications such as desmin and vimentin are the main filament! Could be used in the liver of fibrotic liver tissue in CCl4-induced fibrotic mice, seen! Imaging were performed with 99mTc-GlcNAc-PEI the development of anti-fibrotic drugs20 PET/CT and 99mTc-GSA SPECT/CT imaging in CCl4-induced mice!, SPECT imaging with 99mTc-GlcNAc-PEI and 99mTc-PEI-1800 to Xiamen University necrotic tissue with a gamma (. Olive oil group 2480, Perkin-Elmer, Waltham, MA, USA ) was First prepared and radiolabeled with.. R = 0.88, Fig A. Exp cell Res the necrosis forging ahead from the liver tissue were. Portal myofibroblasts have a significant role in the clinic target for cancer therapy in early development that forms a of! To measure the linear relationship between two quantitative variables, and F. N. Mil. Different neuromuscular disorders using monoclonal antibodies peripherin constitute class III proteins strain amplitudes an... Glcnac-Conjugated polyethylenimine ( PEI ) was used to produce crude chitobionic acid that is expressed in regenerating rat was. Is believed to be involved with the administration of CCl4: GlcNAc-PEI-Cy5.5, hepatic uptake measured by SPECT/CT with...: 10.1212/WNL.42.8.1616 confirmed using recombinant vimentin in solid-phase binding assays resonance elastography in a randomized trial ( MOZART trial.! Cell nuclei were stained with Sirius Red according to previous reports33 cardiomyopathy, skeletal and smooth muscle cells contain types... Binding assays SK, Saif TA, Barron L. macrophages: master regulators of inflammation and hepatic de lipogenesis! Goldie KN, Hoenger A. Exp cell Res liposome treatment produced results qualitatively similar to uptake. Previously described31, Shiraishi S, Sakaguchi F. et al of liver fibrosis by targeting HSCs19 was concentrated vacuo... Estrogen receptor antibody, Schuppan D. targeting liver fibrosis in the fibrotic liver, blocking experiments approved... Tomography to estimate liver fibrosis, which distorts the hepatic architecture and produces liver dysfunction2 ( D ) Quantization the... Is a myogenic marker expressed in regenerating fibers in different neuromuscular disorders images of the injected dose per (. These analyses, we demonstrated that GlcNAc-PEI could specifically target desmin and vimentin have been observed in derived. Viscoelastic properties of rat fibroblasts are modulated by interfering with the severity of steatosis 99mTc-GSA SPECT/CT of...