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Native adiponectin plays a role in the adipocyte-mediated conversion of fibroblasts to myofibroblasts
Journal article   Open access   Peer reviewed

Native adiponectin plays a role in the adipocyte-mediated conversion of fibroblasts to myofibroblasts

Mariam Y El-Hattab, Noah Sinclair, Jesse N Liszewski, Michael V Schrodt, Jacob Herrmann, Aloysius J Klingelhutz, Edward A Sander and James A Ankrum
Journal of the Royal Society interface, Vol.20(202), 20230004
05/2023
DOI: 10.1098/rsif.2023.0004
PMCID: PMC10154927
PMID: 37132228
url
https://doi.org/10.1098/rsif.2023.0004View
Published (Version of record) Open Access

Abstract

Adipocytes regulate tissues through production of adipokines that can act both locally and systemically. Adipocytes also have been found to play a critical role in regulating the healing process. To better understand this role, we developed a three-dimensional human adipocyte spheroid system that has an adipokine profile similar to adipose tissues. Previously, we found that conditioned medium from these spheroids induces human dermal fibroblast conversion into highly contractile, collagen-producing myofibroblasts through a transforming growth factor beta-1 (TGF-β1) independent pathway. Here, we sought to identify how mature adipocytes signal to dermal fibroblasts through adipokines to induce myofibroblast conversion. By using molecular weight fractionation, heat inactivation and lipid depletion, we determined mature adipocytes secrete a factor that is 30-100 kDa, heat labile and lipid associated that induces myofibroblast conversion. We also show that the depletion of the adipokine adiponectin, which fits those physico-chemical parameters, eliminates the ability of adipocyte-conditioned media to induce fibroblast to myofibroblast conversion. Interestingly, native adiponectin secreted by cultured adipocytes consistently elicited a stronger level of α-smooth muscle actin expression than exogenously added adiponectin. Thus, adiponectin secreted by mature adipocytes induces fibroblast to myofibroblast conversion and may lead to a phenotype of myofibroblasts distinct from TGF-β1-induced myofibroblasts.
Bioengineering Biomedical Engineering Biotechnology UIOWA OA Agreement adiponectin adipocytes myofibroblasts α-SMA fractionation

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