Collagen Stiffness and Architecture Regulate Fibrotic Gene Expression in
Engineered Adipose Tissue.
Authors Di Caprio N, Bellas E
Submitted By Submitted Externally on 7/20/2020
Status Published
Journal Advanced biosystems
Year 2020
Date Published 6/1/2020
Volume : Pages 4 : e1900286
PubMed Reference 32529801
Abstract Adipose tissue (AT) has a dynamic extracellular matrix (ECM) surrounding
adipocytes that allows for remodeling during metabolic fluctuations. During the
progression of obesity, AT has increased ECM deposition, stiffening, and
remodeling, resulting in a pro-fibrotic dysfunctional state. Here, the
incorporation of ethylene glycol-bis-succinic acid N-hydroxysuccinimide ester
(PEGDS) allows for control over 3D collagen hydrogel stiffness and architecture
to investigate its influence on adipocyte metabolic and fibrotic function. Upon
stiffening and altering ECM architecture, adipocytes did not alter their
expression of key adipokines, leptin, and adiponectin. However, they do increase
actin cytoskeletal fiber formation, pro-fibrotic gene expression, ECM
deposition, and remodeling within a stiffer, 3D collagen hydrogel. For example,
COL6A3 gene expression is upregulated approximately twofold, resulting in
increased deposition of pericellular collagen VI alpha 3 surrounding adipocytes.
Furthermore, inhibition of actin contractility results in a reversal of
pro-fibrotic gene expression and ECM deposition, indicating that adipocytes are
mediating mechanical cues through actin cytoskeletal networks. This study
demonstrates that ECM stiffness and architecture plays a critical regulatory
role in adipocyte fibrotic function and contributes to the overall pro-fibrotic
dysfunctional state of AT during the progression of obesity and AT fibrosis.