Therapeutic Benefit of Galectin-1: Beyond Membrane Repair, a Multifaceted Approach to LGMD2B

Two of the main pathologies characterizing dysferlinopathies are disrupted muscle membrane repair and chronic inflammation, which lead to symptoms of muscle weakness and wasting. Here, we used recombinant human Galectin-1 (rHsGal-1) as a therapeutic for LGMD2B mouse and human models. Various redox a...

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Autores principales:	Mary L. Vallecillo-Zúniga, Peter Daniel Poulson, Jacob S. Luddington, Christian J. Arnold, Matthew Rathgeber, Braden C. Kartchner, Spencer Hayes, Hailie Gill, Jonard C. Valdoz, Jonathan L. Spallino, Seth Garfield, Ethan L. Dodson, Connie M. Arthur, Sean R. Stowell, Pam M. Van Ry
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Galectin-1 LGMD2B membrane repair NF-ĸB inflammation cytokines Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/91776f7c4f7e4124ac9a89b01315ee53
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spelling	oai:doaj.org-article:91776f7c4f7e4124ac9a89b01315ee532021-11-25T17:12:54ZTherapeutic Benefit of Galectin-1: Beyond Membrane Repair, a Multifaceted Approach to LGMD2B10.3390/cells101132102073-4409https://doaj.org/article/91776f7c4f7e4124ac9a89b01315ee532021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3210https://doaj.org/toc/2073-4409Two of the main pathologies characterizing dysferlinopathies are disrupted muscle membrane repair and chronic inflammation, which lead to symptoms of muscle weakness and wasting. Here, we used recombinant human Galectin-1 (rHsGal-1) as a therapeutic for LGMD2B mouse and human models. Various redox and multimerization states of Gal-1 show that rHsGal-1 is the most effective form in both increasing muscle repair and decreasing inflammation, due to its monomer-dimer equilibrium. Dose-response testing shows an effective 25-fold safety profile between 0.54 and 13.5 mg/kg rHsGal-1 in Bla/J mice. Mice treated weekly with rHsGal-1 showed downregulation of canonical NF-κB inflammation markers, decreased muscle fat deposition, upregulated anti-inflammatory cytokines, increased membrane repair, and increased functional movement compared to non-treated mice. Gal-1 treatment also resulted in a positive self-upregulation loop of increased endogenous Gal-1 expression independent of NF-κB activation. A similar reduction in disease pathologies in patient-derived human cells demonstrates the therapeutic potential of Gal-1 in LGMD2B patients.Mary L. Vallecillo-ZúnigaPeter Daniel PoulsonJacob S. LuddingtonChristian J. ArnoldMatthew RathgeberBraden C. KartchnerSpencer HayesHailie GillJonard C. ValdozJonathan L. SpallinoSeth GarfieldEthan L. DodsonConnie M. ArthurSean R. StowellPam M. Van RyMDPI AGarticleGalectin-1LGMD2Bmembrane repairNF-ĸBinflammationcytokinesBiology (General)QH301-705.5ENCells, Vol 10, Iss 3210, p 3210 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Galectin-1 LGMD2B membrane repair NF-ĸB inflammation cytokines Biology (General) QH301-705.5
spellingShingle	Galectin-1 LGMD2B membrane repair NF-ĸB inflammation cytokines Biology (General) QH301-705.5 Mary L. Vallecillo-Zúniga Peter Daniel Poulson Jacob S. Luddington Christian J. Arnold Matthew Rathgeber Braden C. Kartchner Spencer Hayes Hailie Gill Jonard C. Valdoz Jonathan L. Spallino Seth Garfield Ethan L. Dodson Connie M. Arthur Sean R. Stowell Pam M. Van Ry Therapeutic Benefit of Galectin-1: Beyond Membrane Repair, a Multifaceted Approach to LGMD2B
description	Two of the main pathologies characterizing dysferlinopathies are disrupted muscle membrane repair and chronic inflammation, which lead to symptoms of muscle weakness and wasting. Here, we used recombinant human Galectin-1 (rHsGal-1) as a therapeutic for LGMD2B mouse and human models. Various redox and multimerization states of Gal-1 show that rHsGal-1 is the most effective form in both increasing muscle repair and decreasing inflammation, due to its monomer-dimer equilibrium. Dose-response testing shows an effective 25-fold safety profile between 0.54 and 13.5 mg/kg rHsGal-1 in Bla/J mice. Mice treated weekly with rHsGal-1 showed downregulation of canonical NF-κB inflammation markers, decreased muscle fat deposition, upregulated anti-inflammatory cytokines, increased membrane repair, and increased functional movement compared to non-treated mice. Gal-1 treatment also resulted in a positive self-upregulation loop of increased endogenous Gal-1 expression independent of NF-κB activation. A similar reduction in disease pathologies in patient-derived human cells demonstrates the therapeutic potential of Gal-1 in LGMD2B patients.
format	article
author	Mary L. Vallecillo-Zúniga Peter Daniel Poulson Jacob S. Luddington Christian J. Arnold Matthew Rathgeber Braden C. Kartchner Spencer Hayes Hailie Gill Jonard C. Valdoz Jonathan L. Spallino Seth Garfield Ethan L. Dodson Connie M. Arthur Sean R. Stowell Pam M. Van Ry
author_facet	Mary L. Vallecillo-Zúniga Peter Daniel Poulson Jacob S. Luddington Christian J. Arnold Matthew Rathgeber Braden C. Kartchner Spencer Hayes Hailie Gill Jonard C. Valdoz Jonathan L. Spallino Seth Garfield Ethan L. Dodson Connie M. Arthur Sean R. Stowell Pam M. Van Ry
author_sort	Mary L. Vallecillo-Zúniga
title	Therapeutic Benefit of Galectin-1: Beyond Membrane Repair, a Multifaceted Approach to LGMD2B
title_short	Therapeutic Benefit of Galectin-1: Beyond Membrane Repair, a Multifaceted Approach to LGMD2B
title_full	Therapeutic Benefit of Galectin-1: Beyond Membrane Repair, a Multifaceted Approach to LGMD2B
title_fullStr	Therapeutic Benefit of Galectin-1: Beyond Membrane Repair, a Multifaceted Approach to LGMD2B
title_full_unstemmed	Therapeutic Benefit of Galectin-1: Beyond Membrane Repair, a Multifaceted Approach to LGMD2B
title_sort	therapeutic benefit of galectin-1: beyond membrane repair, a multifaceted approach to lgmd2b
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/91776f7c4f7e4124ac9a89b01315ee53
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Therapeutic Benefit of Galectin-1: Beyond Membrane Repair, a Multifaceted Approach to LGMD2B

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