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3. Tofacitinib Regulates Endostatin via Effects on CD147 and Cathepsin S.

Author

Zisman, Devy, Sabtan, Hala, Rahat, Maya M., Simanovich, Elina, Haddad, Amir, Gazitt, Tal, Feld, Joy, Slobodin, Gleb, Kibari, Adi, Elias, Muna, and Rahat, Michal A.

Subjects
ENDOSTATIN, VASCULAR endothelial growth factors, RHEUMATOID arthritis, GENE expression, MATRIX metalloproteinases, CELL lines
Abstract

Angiogenesis is critical for rheumatoid arthritis (RA) progression. The effects of tofacitinib, a JAK-STAT inhibitor used for RA treatment, on angiogenesis in RA are unclear. We, therefore, evaluated the levels of angiogenic factors in two systems of a human co-culture of fibroblast (HT1080) and monocytic (U937) cell lines treated with tofacitinib and in serum samples from RA patients before and after six months of tofacitinib treatment. Tofacitinib reduced CD147 levels, matrix metalloproteinase-9 (MMP-9) activity, and angiogenic potential but increased endostatin levels and secreted proteasome 20S activity. In vitro, tofacitinib did not change CD147 mRNA but increased miR-146a-5p expression and reduced STAT3 phosphorylation. We recently showed that CD147 regulates the ability of MMP-9 and secreted proteasome 20S to cleave collagen XVIIIA into endostatin. We show here that tofacitinib-enhanced endostatin levels are mediated by CD147, as CD147-siRNA or an anti-CD147 antibody blocked proteasome 20S activity. The correlation between CD147 and different disease severity scores supported this role. Lastly, tofacitinib reduced endostatin' s degradation by inhibiting cathepsin S activity and recombinant cathepsin S reversed this in both systems. Thus, tofacitinib inhibits angiogenesis by reducing pro-angiogenic factors and enhancing the anti-angiogenic factor endostatin in a dual effect mediated partly through CD147 and partly through cathepsin S. [ABSTRACT FROM AUTHOR]

Published
2024
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5. A deep look into the storm: Israeli multi-center experience of coronavirus disease 2019 (COVID-19) in patients with autoimmune inflammatory rheumatic diseases before and after vaccinations

Author

Kharouf, Fadi, primary, Eviatar, Tali, additional, Braun, Maya, additional, Pokroy-Shapira, Elisheva, additional, Brodavka, Michal, additional, Zloof, Yair, additional, Agmon-Levin, Nancy, additional, Toledano, Kochava, additional, Oren, Shirly, additional, Lidar, Merav, additional, Zisman, Devy, additional, Tavor, Yonit, additional, Amit-Vazina, Mirit, additional, Sabbah, Firas, additional, Breuer, Gabriel S., additional, Dagan, Amir, additional, Beshara-Garzuzi, Rima, additional, Markovits, Doron, additional, Elias, Muna, additional, Feld, Joy, additional, Tayer-Shifman, Oshrat, additional, Gazitt, Tal, additional, Reitblatt, Tatiana, additional, Rubin, Limor, additional, Haddad, Amir, additional, Giryes, Sami, additional, Paran, Daphna, additional, Peleg, Hagit, additional, Molad, Yair, additional, Elkayam, Ori, additional, Mevorach, Dror, additional, Balbir-Gurman, Alexandra, additional, and Braun-Moscovici, Yolanda, additional

Published
2023
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6. Development of Autoantibodies Following BNT162b2 mRNA COVID-19 Vaccination and Their Association with Disease Flares in Adult Patients with Autoimmune Inflammatory Rheumatic Diseases (AIIRD) and the General Population: Results of 1-Year Prospective Follow-Up Study

Author

Gazitt, Tal, primary, Eviatar, Tali, additional, Shear, Jacqueline, additional, Meidan, Roni, additional, Furer, Victoria, additional, Feld, Joy, additional, Haddad, Amir, additional, Elias, Muna, additional, Hijazi, Nizar, additional, Stein, Nili, additional, Shaked Mishan, Pninit, additional, Zetser, Anna, additional, Peleg, Hagit, additional, Elkayam, Ori, additional, and Zisman, Devy, additional

Published
2023
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7. Predictors of Immunogenic Response to the BNT162b2 mRNA COVID-19 Vaccination in Patients with Autoimmune Inflammatory Rheumatic Diseases Treated with Rituximab

Author

Furer, Victoria, primary, Eviatar, Tali, additional, Zisman, Devy, additional, Peleg, Hagit, additional, Braun-Moscovici, Yolanda, additional, Balbir-Gurman, Alexandra, additional, Paran, Daphna, additional, Levartovsky, David, additional, Zisapel, Michael, additional, Elalouf, Ofir, additional, Kaufman, Ilana, additional, Broyde, Adi, additional, Polachek, Ari, additional, Feld, Joy, additional, Haddad, Amir, additional, Gazitt, Tal, additional, Elias, Muna, additional, Higazi, Nizar, additional, Kharouf, Fadi, additional, Pel, Sara, additional, Nevo, Sharon, additional, and Elkayam, Ori, additional

Published
2022
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9. Tocilizumab (TCZ) Decreases Angiogenesis in Rheumatoid Arthritis Through Its Regulatory Effect on miR-146a-5p and EMMPRIN/CD147

Author

Zisman, Devy, primary, Safieh, Mirna, additional, Simanovich, Elina, additional, Feld, Joy, additional, Kinarty, Amalia, additional, Zisman, Liron, additional, Gazitt, Tal, additional, Haddad, Amir, additional, Elias, Muna, additional, Rosner, Itzhak, additional, Kaly, Lisa, additional, and Rahat, Michal A., additional

Published
2021
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11. Immune-Mediated Disease Flares or New-Onset Disease in 27 Subjects Following mRNA/DNA SARS-CoV-2 Vaccination

Author

Watad, Abdulla, primary, De Marco, Gabriele, additional, Mahajna, Hussein, additional, Druyan, Amit, additional, Eltity, Mailam, additional, Hijazi, Nizar, additional, Haddad, Amir, additional, Elias, Muna, additional, Zisman, Devy, additional, Naffaa, Mohammad E., additional, Brodavka, Michal, additional, Cohen, Yael, additional, Abu-Much, Arsalan, additional, Abu Elhija, Muhanad, additional, Bridgewood, Charlie, additional, Langevitz, Pnina, additional, McLorinan, Joanna, additional, Bragazzi, Nicola Luigi, additional, Marzo-Ortega, Helena, additional, Lidar, Merav, additional, Calabrese, Cassandra, additional, Calabrese, Leonard, additional, Vital, Edward, additional, Shoenfeld, Yehuda, additional, Amital, Howard, additional, and McGonagle, Dennis, additional

Published
2021
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