Lactoferrin Contributes a Renoprotective Effect in Acute Kidney Injury and Early Renal Fibrosis

Patients with acute kidney injury (AKI) who survive the acute stage are at notable risk for chronic kidney disease (CKD) progression. There is no single therapy that can effectively prevent the AKI to CKD transition. Autophagy is a cytoplasmic component degradation pathway and has complex functions...

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Bibliographic Details
Published in:Pharmaceutics 2020-05, Vol.12 (5), p.434
Main Authors: Hsu, Yung-Ho, Chiu, I-Jen, Lin, Yuh-Feng, Chen, Yi-Jie, Lee, Yu-Hsuan, Chiu, Hui-Wen
Format: Article
Language:English
Subjects:
Acids
acute kidney injury
Apoptosis
Autophagy
Cell cycle
chronic kidney disease
fibrosis
Gene expression
Immunoglobulins
Inflammation
Kidney diseases
Laboratory animals
lactoferrin
Oxidative stress
Proteins
Variance analysis
Vitamin B
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Summary:Patients with acute kidney injury (AKI) who survive the acute stage are at notable risk for chronic kidney disease (CKD) progression. There is no single therapy that can effectively prevent the AKI to CKD transition. Autophagy is a cytoplasmic component degradation pathway and has complex functions in several diseases, such as renal fibrosis. Previous research has shown that lactoferrin has important functions in antioxidant defense and other defense systems, protecting kidneys against various injuries. The present study investigated the effect of lactoferrin in protecting against the AKI to CKD transition. We identified 62 consensus genes with two-fold changes in clinical kidney tissues from AKI and CKD patients. Among the 62 overlay genes, the mRNA levels of LTF were significantly upregulated in the kidney tissues of AKI and CKD patients. Lactoferrin induced autophagy via the activation of the AMPK and inhibition of Akt/mTOR pathway in human kidney proximal tubular cells. Lactoferrin suppressed oxidative stress-induced cell death and apoptosis by augmenting autophagy. Lactoferrin has an antifibrotic role in human kidney tubular cells. In a mouse model of folic acid-induced AKI to CKD transition, treatment with lactoferrin recovered renal function and further suppressed renal fibrosis through the inhibition of apoptosis and the induction of autophagy. These findings identify lactoferrin as a potential therapeutic target for the prevention of the AKI to CKD transition.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics12050434