FSTL1 aggravates sepsis-induced acute kidney injury through regulating TLR4/MyD88/NF-κB pathway in newborn rats
1Department of Paediatric Intensive Care Unit (PICU), the First Aﬃliated Hospital of Xinjiang Medical University, 830054 Urumqi City, Xinjiang Uygur Autonomous Region, China
DOI: 10.22514/sv.2021.071 Vol.17,Issue 3,May 2021 pp.167-173
Submitted: 05 February 2021 Accepted: 06 April 2021
Published: 08 May 2021
Background: The aim of this work was to investigate whether Follistatin like 1 (FSTL1) exerted an effect on acute kidney injury (AKI) induced by sepsis, and to explore the molecular mechanism.
Methods: A cecal ligation and puncture (CLP) model was established and adenoviral solution was administrated to newborn rats to achieve FSTL1 knockdown. Colorimetric assays measured concentrations of serum creatinine and blood urea nitrogen (BUN) and ELISA assays were performed to examine TNF-α, IL-1β and IL-6 levels in serum and kidney tissues. Kidney histological analysis was performed using hematoxylin-eosin (HE) staining. Protein levels of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), phosphorylated p65 (p-p65) and total p65 (p65) were determined by western blotting.
Results: FSTL1 was significantly up-regulated in kidneys following CLP, but subsequent FSTL1 inhibition alleviated AKI. FSTL1 knockdown following CLP inhibited the production of TNF-α, IL-1β, IL-6 and inactivated the TLR4/MyD88/NF-κB pathway. Furthermore, FSTL1 overexpression activated the TLR4/MyD88/NF-κB pathway following CLP, but TLR4 inhibitor TAK242 abolished this effect.
Conclusions: FSTL1 aggravates sepsis-induced acute kidney injury through regulating the TLR4/MyD88/NF-κB pathway.
FSTL1; Sepsis; Acute kidney injury; NF-κB
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