Evaluation of the Effects of CCN4 on Pancreatic Beta Cell Proliferation

Overview

Journal Methods Mol Biol

Specialty Molecular Biology

Date 2022 Nov 12

PMID 36370351

Authors

Rebeca Fernandez-Ruiz

Rosa Gasa

Affiliations

Soon will be listed here.

Abstract

Expanding the number of insulin-producing beta cells through reactivation of their replication has been proposed as a therapy to prevent or delay the appearance of diabetes. Using antibody arrays, we identified CCN4/Wisp1 as a circulating factor enriched in preweaning mice, a period in which beta cells exhibit a dramatic increase in number. This finding led us to investigate the involvement of CCN4 in beta cell proliferation. We demonstrated that CCN4 promotes adult beta cell proliferation in vitro in cultured isolated islets, and in vivo in islets transplanted into the anterior chamber of the eye. In this chapter, we present the methodology that was used to study proliferation in both settings.

References

Wang P, Fiaschi-Taesch N, Vasavada R, Scott D, Garcia-Ocana A, Stewart A . Diabetes mellitus--advances and challenges in human β-cell proliferation. Nat Rev Endocrinol. 2015; 11(4):201-12. DOI: 10.1038/nrendo.2015.9. View

Conboy I, Conboy M, Wagers A, Girma E, Weissman I, Rando T . Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature. 2005; 433(7027):760-4. DOI: 10.1038/nature03260. View

Song G, Nguyen D, Pietramaggiori G, Scherer S, Chen B, Zhan Q . Use of the parabiotic model in studies of cutaneous wound healing to define the participation of circulating cells. Wound Repair Regen. 2010; 18(4):426-32. PMC: 2935287. DOI: 10.1111/j.1524-475X.2010.00595.x. View

Villeda S, Luo J, Mosher K, Zou B, Britschgi M, Bieri G . The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature. 2011; 477(7362):90-4. PMC: 3170097. DOI: 10.1038/nature10357. View

Riley K, Pasek R, Maulis M, Peek J, Thorel F, Brigstock D . Connective tissue growth factor modulates adult β-cell maturity and proliferation to promote β-cell regeneration in mice. Diabetes. 2014; 64(4):1284-98. PMC: 4375083. DOI: 10.2337/db14-1195. View

Bornstein P . Matricellular proteins: an overview. J Cell Commun Signal. 2009; 3(3-4):163-5. PMC: 2778588. DOI: 10.1007/s12079-009-0069-z. View

Stephens S, Palmer J, Konstantinova I, Pearce A, Jarai G, Day E . A functional analysis of Wnt inducible signalling pathway protein -1 (WISP-1/CCN4). J Cell Commun Signal. 2015; 9(1):63-72. PMC: 4414832. DOI: 10.1007/s12079-015-0267-9. View

Viloria K, Hill N . Embracing the complexity of matricellular proteins: the functional and clinical significance of splice variation. Biomol Concepts. 2016; 7(2):117-32. DOI: 10.1515/bmc-2016-0004. View

Gerarduzzi C, Hartmann U, Leask A, Drobetsky E . The Matrix Revolution: Matricellular Proteins and Restructuring of the Cancer Microenvironment. Cancer Res. 2020; 80(13):2705-2717. DOI: 10.1158/0008-5472.CAN-18-2098. View

10.

Frangogiannis N . Matricellular proteins in cardiac adaptation and disease. Physiol Rev. 2012; 92(2):635-88. PMC: 4411042. DOI: 10.1152/physrev.00008.2011. View

11.

Yeger H, Perbal B . The CCN family of genes: a perspective on CCN biology and therapeutic potential. J Cell Commun Signal. 2008; 1(3-4):159-64. PMC: 2443235. DOI: 10.1007/s12079-008-0022-6. View

12.

Fernandez-Ruiz R, Garcia-Alaman A, Esteban Y, Mir-Coll J, Serra-Navarro B, Fontcuberta-PiSunyer M . Wisp1 is a circulating factor that stimulates proliferation of adult mouse and human beta cells. Nat Commun. 2020; 11(1):5982. PMC: 7689468. DOI: 10.1038/s41467-020-19657-1. View

13.

Maeda A, Ono M, Holmbeck K, Li L, Kilts T, Kram V . WNT1-induced Secreted Protein-1 (WISP1), a Novel Regulator of Bone Turnover and Wnt Signaling. J Biol Chem. 2015; 290(22):14004-18. PMC: 4447973. DOI: 10.1074/jbc.M114.628818. View

14.

Murahovschi V, Pivovarova O, Ilkavets I, Dmitrieva R, Docke S, Keyhani-Nejad F . WISP1 is a novel adipokine linked to inflammation in obesity. Diabetes. 2014; 64(3):856-66. DOI: 10.2337/db14-0444. View

15.

Corbin K, West H, Brodsky S, Whitticar N, Koch W, Nunemaker C . A Practical Guide to Rodent Islet Isolation and Assessment Revisited. Biol Proced Online. 2021; 23(1):7. PMC: 7919091. DOI: 10.1186/s12575-021-00143-x. View

16.

Speier S, Nyqvist D, Kohler M, Caicedo A, Leibiger I, Berggren P . Noninvasive high-resolution in vivo imaging of cell biology in the anterior chamber of the mouse eye. Nat Protoc. 2008; 3(8):1278-86. PMC: 3538838. DOI: 10.1038/nprot.2008.118. View