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Your search keyword '"Vijay Krishna Raghunathan"' showing total 2 results
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2 results on '"Vijay Krishna Raghunathan"'

1. Glucocorticoid-induced cell-derived matrix modulates transforming growth factor β2 signaling in human trabecular meshwork cells

Author

Felix Yemanyi, Janice Vranka, and Vijay Krishna Raghunathan

Subjects
Medicine, Science
Abstract

Abstract Aberrant remodeling of trabecular meshwork (TM) extracellular matrix (ECM) may induce ocular hypertensive phenotypes in human TM (hTM) cells to cause ocular hypertension, via a yet unknown mechanism. Here, we show that, in the absence of exogenous transforming growth factor-beta2 (TGFβ2), compared with control matrices (VehMs), glucocorticoid-induced cell-derived matrices (GIMs) trigger non-Smad TGFβ2 signaling in hTM cells, correlated with overexpression/activity of structural ECM genes (fibronectin, collagen IV, collagen VI, myocilin), matricellular genes (connective tissue growth factor [CTGF], secreted protein, acidic and rich in cysteine), crosslinking genes/enzymes (lysyl oxidase, lysyl oxidase-like 2–4, tissue transglutaminase-2), and ECM turnover genes/enzymes (matrix metalloproteinases-MMP2,14 and their inhibitors-TIMP2). However, in the presence of exogenous TGFβ2, VehMs and GIMs activate Smad and non-Smad TGFβ2 signaling in hTM cells, associated with overexpression of α-smooth muscle actin (α-SMA), and differential upregulation of aforementioned ECM genes/proteins with new ones emerging (collagen-I, thrombospondin-I, plasminogen activator inhibitor, MMP1, 9, ADAMTS4, TIMP1); with GIM-TGFβ2-induced changes being mostly more pronounced. This suggests dual glaucomatous insults potentiate profibrotic signaling/phenotypes. Lastly, we demonstrate type I TGFβ receptor kinase inhibition abrogates VehM-/GIM- and/or TGFβ2-induced upregulation of α-SMA and CTGF. Collectively, pathological TM microenvironments are sufficient to elicit adverse cellular responses that may be ameliorated by targeting TGFβ2 pathway.

Published
2020
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2. Early redox activities modulate Xenopus tail regeneration

Author

Vijay Krishna Raghunathan, Kan Zhu, Min Zhao, Fernando Ferreira, and Guillaume Luxardi

Subjects
0301 basic medicine, Male, De facto, Xenopus, General Physics and Astronomy, Xenopus Proteins, Regenerative Medicine, Oxygen, Macrocyclic, Animals, Genetically Modified, Mice, Ros scavenging, Xenopus laevis, Benzoquinones, lcsh:Science, Skin, chemistry.chemical_classification, Multidisciplinary, biology, Cell Hypoxia, Cell biology, Mutant Strains, Larva, Female, Hypoxia-Inducible Factor 1, Oxidation-Reduction, Tail, Lactams, Lactams, Macrocyclic, Science, chemistry.chemical_element, Genetically Modified, Echinomycin, alpha Subunit, Redox, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Heat shock protein, Animals, Regeneration, HSP90 Heat-Shock Proteins, Reactive oxygen species, Oxidation reduction, General Chemistry, biology.organism_classification, Hypoxia-Inducible Factor 1, alpha Subunit, Mice, Mutant Strains, 030104 developmental biology, chemistry, lcsh:Q, Reactive Oxygen Species
Abstract

Redox state sustained by reactive oxygen species (ROS) is crucial for regeneration; however, the interplay between oxygen (O2), ROS and hypoxia-inducible factors (HIF) remains elusive. Here we observe, using an optic-based probe (optrode), an elevated and steady O2 influx immediately upon amputation. The spatiotemporal O2 influx profile correlates with the regeneration of Xenopus laevis tadpole tails. Inhibition of ROS production but not ROS scavenging decreases O2 influx. Inhibition of HIF-1α impairs regeneration and stabilization of HIF-1α induces regeneration in the refractory period. In the regeneration bud, hypoxia correlates with O2 influx, ROS production, and HIF-1α stabilization that modulate regeneration. Further analyses reveal that heat shock protein 90 is a putative downstream target of HIF-1α while electric current reversal is a de facto downstream target of HIF-1α. Collectively, the results show a mechanism for regeneration via the orchestration of O2 influx, ROS production, and HIF-1α stabilization., Reactive oxygen species (ROS) and hypoxia-inducible factors (HIF) mediate regeneration but how is unclear. Here, the authors use an optic-based probe (‘optrode’) to monitor oxygen (O2) during Xenopus tail regeneration, identifying crosstalk between O2 influx, ROS production, and HIF-1α stabilization.

Published
2018

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