HSP70-Mediated NLRP3 Inflammasome Suppression Underlies Reversal of Acute Kidney Injury Following Extracellular Vesicle and Focused Ultrasound Combination Therapy

Autor: Daniel D. Liu, Sravanthi Rai, Mujib Ullah, Avnesh S. Thakor, Waldo Concepcion
Rok vydání: 2020
Předmět:
Stromal cell
Combination therapy
Inflammasomes
Ultrasonic Therapy
heat shock protein
regenerative medicine
Inflammation
Mesenchymal Stem Cell Transplantation
urologic and male genital diseases
Article
Catalysis
lcsh:Chemistry
Inorganic Chemistry
Extracellular Vesicles
Mice
inflammasome
Heat shock protein
NLR Family
Pyrin Domain-Containing 3 Protein
Animals
Medicine
HSP70 Heat-Shock Proteins
Physical and Theoretical Chemistry
lcsh:QH301-705.5
Molecular Biology
Spectroscopy
urogenital system
business.industry
Organic Chemistry
Mesenchymal stem cell
Acute kidney injury
Mesenchymal Stem Cells
Inflammasome
General Medicine
Extracellular vesicle
Acute Kidney Injury
medicine.disease
Combined Modality Therapy
Computer Science Applications
Disease Models
Animal
lcsh:Biology (General)
lcsh:QD1-999
Cancer research
focused ultrasound
medicine.symptom
mesenchymal stromal cells
business
medicine.drug
Zdroj: International Journal of Molecular Sciences
Volume 21
Issue 11
International Journal of Molecular Sciences, Vol 21, Iss 4085, p 4085 (2020)
ISSN: 1422-0067
Popis: Acute kidney injury (AKI) is the abrupt loss of renal function, for which only supportive therapies exist. Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) have been shown to be therapeutically effective in treating AKI by spurring endogenous cell proliferation and survival while suppressing inflammation. Pre-treating kidneys with pulsed focused ultrasound (pFUS) has also been shown to enhance MSC therapy for AKI, but its role in MSC-derived EV therapy remains unexplored. Using a mouse model of cisplatin-induced AKI, we show that combination therapy with pFUS and EVs restores physiological and molecular markers of kidney function, more so than either alone. Both pFUS and EVs downregulate heat shock protein 70 (HSP70), the NLRP3 inflammasome, and its downstream pro-inflammatory cytokines IL-1&beta
and IL-18, all of which are highly upregulated in AKI. In vitro knockdown studies suggest that HSP70 is a positive regulator of the NLRP3 inflammasome. Our study therefore demonstrates the ability of pFUS to enhance EV therapy for AKI and provides further mechanistic understanding of their anti-inflammatory and regenerative effects.
Databáze: OpenAIRE
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