Quantifying the progression of non-alcoholic fatty liver disease in human biomimetic liver microphysiology systems with fluorescent protein biosensors.
Fluorescent protein biosensors
metabolic dysfunction-associated fatty liver disease
metabolic syndrome
microphysiology systems
non-alcoholic fatty liver disease
quantitative systems pharmacology
type 2 diabetes
Journal
Experimental biology and medicine (Maywood, N.J.)
ISSN: 1535-3699
Titre abrégé: Exp Biol Med (Maywood)
Pays: England
ID NLM: 100973463
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
pubmed:
8
5
2021
medline:
15
12
2021
entrez:
7
5
2021
Statut:
ppublish
Résumé
Metabolic syndrome is a complex disease that involves multiple organ systems including a critical role for the liver. Non-alcoholic fatty liver disease (NAFLD) is a key component of the metabolic syndrome and fatty liver is linked to a range of metabolic dysfunctions that occur in approximately 25% of the population. A panel of experts recently agreed that the acronym, NAFLD, did not properly characterize this heterogeneous disease given the associated metabolic abnormalities such as type 2 diabetes mellitus (T2D), obesity, and hypertension. Therefore, metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed as the new term to cover the heterogeneity identified in the NAFLD patient population. Although many rodent models of NAFLD/NASH have been developed, they do not recapitulate the full disease spectrum in patients. Therefore, a platform has evolved initially focused on human biomimetic liver microphysiology systems that integrates fluorescent protein biosensors along with other key metrics, the microphysiology systems database, and quantitative systems pharmacology. Quantitative systems pharmacology is being applied to investigate the mechanisms of NAFLD/MAFLD progression to select molecular targets for fluorescent protein biosensors, to integrate computational and experimental methods to predict drugs for repurposing, and to facilitate novel drug development. Fluorescent protein biosensors are critical components of the platform since they enable monitoring of the pathophysiology of disease progression by defining and quantifying the temporal and spatial dynamics of protein functions in the biosensor cells, and serve as minimally invasive biomarkers of the physiological state of the microphysiology system experimental disease models. Here, we summarize the progress in developing human microphysiology system disease models of NAFLD/MAFLD from several laboratories, developing fluorescent protein biosensors to monitor and to measure NAFLD/MAFLD disease progression and implementation of quantitative systems pharmacology with the goal of repurposing drugs and guiding the creation of novel therapeutics.
Identifiants
pubmed: 33957803
doi: 10.1177/15353702211009228
pmc: PMC8606957
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
2420-2441Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK097160
Pays : United States
Organisme : NCATS NIH HHS
ID : U01 TR002383
Pays : United States
Organisme : NIDDK NIH HHS
ID : UH3 DK119973
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK130499
Pays : United States
Organisme : NIH HHS
ID : S10 OD028450
Pays : United States
Organisme : NCATS NIH HHS
ID : U24 TR002632
Pays : United States
Organisme : NCATS NIH HHS
ID : UG3 TR003289
Pays : United States
Organisme : NIH HHS
ID : S10 OD012269
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK120531
Pays : United States
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