scholarly journals Depletion of transglutaminase 2 in neurons alters expression of extracellular matrix and signal transduction genes and compromises cell viability

2018 ◽  
Vol 86 ◽  
pp. 72-80 ◽  
Author(s):  
Laura Yunes-Medina ◽  
Alex Paciorkowski ◽  
Yan Nuzbrokh ◽  
Gail V.W. Johnson
Keyword(s):  
Signal Transduction ◽  
Extracellular Matrix ◽  
Cell Viability ◽  
Transglutaminase 2 ◽  
Signal Transduction Genes

scholarly journals Bioprinting Via a Dual-Gel Bioink Based on Poly(Vinyl Alcohol) and Solubilized Extracellular Matrix towards Cartilage Engineering

2021 ◽  
Vol 22 (8) ◽  
pp. 3901
Author(s):  
Mohsen Setayeshmehr ◽  
Shahzad Hafeez ◽  
Clemens van Blitterswijk ◽  
Lorenzo Moroni ◽  
Carlos Mota ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Viability ◽  
Vinyl Alcohol ◽  
Compression Modulus ◽  
Synthetic Polymers ◽  
Poly Vinyl Alcohol ◽  
Cross Linking ◽  
Light Curing ◽  
Shape Retention ◽  
Amine Groups

Various hydrogel systems have been developed as biomaterial inks for bioprinting, including natural and synthetic polymers. However, the available biomaterial inks, which allow printability, cell viability, and user-defined customization, remains limited. Incorporation of biological extracellular matrix materials into tunable synthetic polymers can merge the benefits of both systems towards versatile materials for biofabrication. The aim of this study was to develop novel, cell compatible dual-component biomaterial inks and bioinks based on poly(vinyl alcohol) (PVA) and solubilized decellularized cartilage matrix (SDCM) hydrogels that can be utilized for cartilage bioprinting. In a first approach, PVA was modified with amine groups (PVA-A), and mixed with SDCM. The printability of the PVA-A/SDCM formulations cross-linked by genipin was evaluated. On the second approach, the PVA was functionalized with cis-5-norbornene-endo-2,3-dicarboxylic anhydride (PVA-Nb) to allow an ultrafast light-curing thiol-ene cross-linking. Comprehensive experiments were conducted to evaluate the influence of the SDCM ratio in mechanical properties, water uptake, swelling, cell viability, and printability of the PVA-based formulations. The studies performed with the PVA-A/SDCM formulations cross-linked by genipin showed printability, but poor shape retention due to slow cross-linking kinetics. On the other hand, the PVA-Nb/SDCM showed good printability. The results showed that incorporation of SDCM into PVA-Nb reduces the compression modulus, enhance cell viability, and bioprintability and modulate the swelling ratio of the resulted hydrogels. Results indicated that PVA-Nb hydrogels containing SDCM could be considered as versatile bioinks for cartilage bioprinting.

scholarly journals MiR-144-3p Aggravated Cartilage Injury in Rheumatoid Arthritis by Regulating BMP2/PI3K/Akt Axis

2021 ◽  
Author(s):  
Mei-Li Mo ◽  
Jin-Mei Jiang ◽  
Xiao-Ping Long ◽  
Li-Hu Xie
Keyword(s):  
Extracellular Matrix ◽  
Cell Viability ◽  
Cell Injury ◽  
Tissue Injury ◽  
Cartilage Injury ◽  
Luciferase Assay ◽  
Tunel Staining ◽  
Western Blots

Abstract Objectives Present study aimed to illustrate the role of miR-144-3p in RA. Methods N1511 chondrocytes were stimulated by IL-1β to mimic RA injury model in vitro. Rats were subjected to injection of type II collagen to establish an in vivo RA model and the arthritis index score was calculated. Cell viability was determined by CCK-8. The expression of cartilage extracellular matrix proteins (Collagen II and Aggrecan) and matrix metalloproteinases protein (MMP-13) were determined by qRT-PCR and western blots. Cell apoptosis was measured by Flow cytometry. ELISA was applied to test the secretion of pro-inflammatory cytokines (IL-1β and TNF-α). Tissue injury and apoptosis were detected by HE staining and TUNEL staining. Interaction of miR-144-3p and BMP2 was verified by dual luciferase assay. Results MiR-144-3p was dramatically increased in IL-1β induced N1511 cells. MiR-144-3p depletion elevated cell viability, suppressed apoptosis, pro-inflammatory cytokine releasing, and extracellular matrix loss in IL-1β induced N1511 cells. Moreover, miR-144-3p targeted BMP2 to modulate its expression negatively. Activation of PI3K/Akt signaling compromised inhibition of BMP2 induced aggravated N1511 cell injury with IL-1β stimulation. Inhibition of miR-144-3p alleviated cartilage injury and inflammatory in RA rats. Conclusion Collectively, miR-144-3p could aggravate chondrocytes injury inflammatory response in RA via BMP2/PI3K/Akt axis.

scholarly journals Transglutaminase 2-Mediated p53 Depletion Promotes Angiogenesis by Increasing HIF-1α-p300 Binding in Renal Cell Carcinoma

2020 ◽  
Vol 21 (14) ◽  
pp. 5042
Author(s):  
Seon-Hyeong Lee ◽  
Joon Hee Kang ◽  
Ji Sun Ha ◽  
Jae-Seon Lee ◽  
Su-Jin Oh ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Renal Cell ◽  
Nuclear Translocation ◽  
Xenograft Model ◽  
Transglutaminase 2 ◽  
P300 Binding

Angiogenesis and the expression of vascular endothelial growth factor (VEGF) are increased in renal cell carcinoma (RCC). Transglutaminase 2 (TGase 2), which promotes angiogenesis in endothelial cells during wound healing, is upregulated in RCC. Tumor angiogenesis involves three domains: cancer cells, the extracellular matrix, and endothelial cells. TGase 2 stabilizes VEGF in the extracellular matrix and promotes VEGFR-2 nuclear translocation in endothelial cells. However, the role of TGase 2 in angiogenesis in the cancer cell domain remains unclear. Hypoxia-inducible factor (HIF)-1α-mediated VEGF production underlies the induction of angiogenesis in cancer cells. In this study, we show that p53 downregulated HIF-1α in RCC, and p53 overexpression decreased VEGF production. Increased TGase 2 promoted angiogenesis by inducing p53 degradation, leading to the activation of HIF-1α. The interaction of HIF-1α and p53 with the cofactor p300 is required for stable transcriptional activation. We found that TGase 2-mediated p53 depletion increased the availability of p300 for HIF-1α-p300 binding. A preclinical xenograft model suggested that TGase 2 inhibition can reverse angiogenesis in RCC.

scholarly journals Thioredoxin-1 Selectively Activates Transglutaminase 2 in the Extracellular Matrix of the Small Intestine

2016 ◽  
Vol 292 (5) ◽  
pp. 2000-2008 ◽  
Author(s):  
Nicholas M. Plugis ◽  
Brad A. Palanski ◽  
Chih-Hisang Weng ◽  
Megan Albertelli ◽  
Chaitan Khosla
Keyword(s):  
Extracellular Matrix ◽  
Small Intestine ◽  
Transglutaminase 2 ◽  
Thioredoxin 1

scholarly journals Transglutaminase 2 in pulmonary and cardiac tissue remodeling in experimental pulmonary hypertension

2017 ◽  
Vol 313 (5) ◽  
pp. L752-L762 ◽  
Author(s):  
Krishna C. Penumatsa ◽  
Deniz Toksoz ◽  
Rod R. Warburton ◽  
Mousa Kharnaf ◽  
Ioana R. Preston ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Pulmonary Hypertension ◽  
Transglutaminase 2 ◽  
Cross Linking ◽  
Matrix Remodeling ◽  
Adventitial Fibroblasts ◽  
Tissue Matrix ◽  
Expression And Activity ◽  
Protein Cross Linking

Tissue matrix remodeling and fibrosis leading to loss of pulmonary arterial and right ventricular compliance are important features of both experimental and clinical pulmonary hypertension (PH). We have previously reported that transglutaminase 2 (TG2) is involved in PH development while others have shown it to be a cross-linking enzyme that participates in remodeling of extracellular matrix in fibrotic diseases in general. In the present studies, we used a mouse model of experimental PH (Sugen 5416 and hypoxia; SuHypoxia) and cultured primary human cardiac and pulmonary artery adventitial fibroblasts to evaluate the relationship of TG2 to the processes of fibrosis, protein cross-linking, extracellular matrix collagen accumulation, and fibroblast-to-myofibroblast transformation. We report here that TG2 expression and activity as measured by serotonylated fibronectin and protein cross-linking activity along with fibrogenic markers are significantly elevated in lungs and right ventricles of SuHypoxic mice with PH. Similarly, TG2 expression and activity, protein cross-linking activity, and fibrogenic markers are significantly increased in cultured cardiac and pulmonary artery adventitial fibroblasts in response to hypoxia exposure. Pharmacological inhibition of TG2 activity with ERW1041E significantly reduced hypoxia-induced cross-linking activity and synthesis of collagen 1 and α-smooth muscle actin in both the in vivo and in vitro studies. TG2 short interfering RNA had a similar effect in vitro. Our results suggest that TG2 plays an important role in hypoxia-induced pulmonary and right ventricular tissue matrix remodeling in the development of PH.

Sign in / Sign up

Export Citation Format

Share Document