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Your search keyword '"Diptiman Chanda"' showing total 4 results
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4 results on '"Diptiman Chanda"'

1. Integrated bioinformatics analysis identifies established and novel TGFβ1-regulated genes modulated by anti-fibrotic drugs

Author

Ava C. Wilson, Joe Chiles, Shah Ashish, Diptiman Chanda, Preeti L. Kumar, James A. Mobley, Enid R. Neptune, Victor J. Thannickal, and Merry-Lynn N. McDonald

Subjects
Medicine, Science
Abstract

Abstract Fibrosis is a leading cause of morbidity and mortality worldwide. Although fibrosis may involve different organ systems, transforming growth factor-β (TGFβ) has been established as a master regulator of fibrosis across organs. Pirfenidone and Nintedanib are the only currently-approved drugs to treat fibrosis, specifically idiopathic pulmonary fibrosis, but their mechanisms of action remain poorly understood. To identify novel drug targets and uncover potential mechanisms by which these drugs attenuate fibrosis, we performed an integrative ‘omics analysis of transcriptomic and proteomic responses to TGFβ1-stimulated lung fibroblasts. Significant findings were annotated as associated with pirfenidone and nintedanib treatment in silico via Coremine. Integrative ‘omics identified a co-expressed transcriptomic and proteomic module significantly correlated with TGFβ1 treatment that was enriched (FDR-p = 0.04) with genes associated with pirfenidone and nintedanib treatment. While a subset of genes in this module have been implicated in fibrogenesis, several novel TGFβ1 signaling targets were identified. Specifically, four genes (BASP1, HSD17B6, CDH11, and TNS1) have been associated with pirfenidone, while five genes (CLINT1, CADM1, MTDH, SYDE1, and MCTS1) have been associated with nintedanib, and MYDGF has been implicated with treatment using both drugs. Using the Clue Drug Repurposing Hub, succinic acid was highlighted as a metabolite regulated by the protein encoded by HSD17B6 . This study provides new insights into the anti-fibrotic actions of pirfenidone and nintedanib and identifies novel targets for future mechanistic studies.

Published
2022
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3. Data from Therapeutic Potential of Adult Bone Marrow–Derived Mesenchymal Stem Cells in Prostate Cancer Bone Metastasis

Author

Selvarangan Ponnazhagan, Matthew S. Beatty, Gene P. Siegal, Girish Ramaswamy, Anandi Sawant, Jonathan A. Hensel, Sanjay Kumar, Tatyana Isayeva, and Diptiman Chanda

Abstract

Purpose: Current evidence indicates that an osteoblast lesion in prostate cancer is preceded by osteolysis. Thus, prevention of osteolysis would reduce complications of bone metastasis. Bone marrow–derived mesenchymal stem cells have the ability to differentiate into osteoblast and produce osteoprotegerin, a decoy receptor for the receptor activator for nuclear factor κB ligand, naturally. The present study examined the potential of unmodified mesenchymal stem cells to prevent osteolytic bone lesions in a preclinical mouse model of prostate cancer.Experimental Design: The human prostate cancer cell line PC3 was implanted in tibiae of severe combined immunodeficient mice. After establishment of the tumor, either unmodified or genetically engineered mesenchymal stem cells overexpressing osteoprotegerin was injected at the site of tumor growth. The effects of therapy were monitored by bioluminescence imaging, micro–computed tomography, immunohistochemistry, and histomorphometry.Results: Data indicated significant (P < 0.001) inhibition of tumor growth and restoration of bone in mice treated with unmodified and modified mesenchymal stem cells. Detailed analysis suggested that the donor mesenchymal stem cell inhibited tumor progression by producing woven bone around the growing tumor cells in the tibiae and by preventing osteoclastogenesis.Conclusions: Overcoming the limitation of the number of mesenchymal stem cells available in the bone can provide significant amelioration for osteolytic damage without further modification. (Clin Cancer Res 2009;15(23):7175–85)

Published
2023
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4. Mitochondrial uncoupling protein-2 reprograms metabolism to induce oxidative stress and myofibroblast senescence in age-associated lung fibrosis

Author

Sunad Rangarajan, Morgan L. Locy, Diptiman Chanda, Ashish Kurundkar, Deepali Kurundkar, Jennifer L. Larson‐Casey, Pilar Londono, Rushita A. Bagchi, Brian Deskin, Hanan Elajaili, Eva S. Nozik, Jessy S. Deshane, Jaroslaw W. Zmijewski, Oliver Eickelberg, and Victor J. Thannickal

Subjects
Aging, Cell Biology, Fibroblasts, Fibrosis, Idiopathic Pulmonary Fibrosis, Mice, Oxidative Stress, Animals, Humans, Uncoupling Protein 2, Myofibroblasts, Reactive Oxygen Species, Lung, Aged
Abstract

Mitochondrial dysfunction has been associated with age-related diseases, including idiopathic pulmonary fibrosis (IPF). We provide evidence that implicates chronic elevation of the mitochondrial anion carrier protein, uncoupling protein-2 (UCP2), in increased generation of reactive oxygen species, altered redox state and cellular bioenergetics, impaired fatty acid oxidation, and induction of myofibroblast senescence. This pro-oxidant senescence reprogramming occurs in concert with conventional actions of UCP2 as an uncoupler of oxidative phosphorylation with dissipation of the mitochondrial membrane potential. UCP2 is highly expressed in human IPF lung myofibroblasts and in aged fibroblasts. In an aging murine model of lung fibrosis, the in vivo silencing of UCP2 induces fibrosis regression. These studies indicate a pro-fibrotic function of UCP2 in chronic lung disease and support its therapeutic targeting in age-related diseases associated with impaired tissue regeneration and organ fibrosis.

Published
2022

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