@article{92bc3c0b45ff412086aaa58d3eabb8d6,
title = "Lactoferrin contributes a renoprotective effect in acute kidney injury and early renal fibrosis",
abstract = "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 toCKDtransition. 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.",
keywords = "Acute kidney injury, Autophagy, Chronic kidney disease, Fibrosis, Lactoferrin",
author = "Hsu, {Yung Ho} and Chiu, {I. Jen} and Lin, {Yuh Feng} and Chen, {Yi Jie} and Lee, {Yu Hsuan} and Chiu, {Hui Wen}",
note = "Funding Information: Figure S1: FA induces renal fibrosis. Representative kidney sections in mice were stained with Masson{\textquoteright}s trichrome renal fibrosis. Representative kidney sections in mice were stained with Masson{\textquoteright}s trichrome staining and staining and examined by microscopy. Scale bar = 60 µm; Figure S2: Immunohistochemistry (IHC) of fibrotic marker protein α-SMA in kidney of FA mouse model. The protein expression of α-SMA in the indicated groups of kidαn-SeMy Ase citnio knisd.nSecya loef bFaAr =m6o0uµsem m; Toadbelel. ST1h: eT hperoitdeeinn teifxicparteisosnioonf 6o2f oαv-SeMrlaAy igne nthese winidthic2a-tfeodldgcrohuanpgs eosf inkitdhneey sections. Scale bar = 60 μm; Table S1: The identification of 62 overlay genes with 2-fold changes in the kidney AutitshsouresC oofnAtrKibI uatniodn Cs:KDCo pnacteiepntutsa. lization, I.-J.C.; Data curation, Y.-H.H., I.-J.C., Y.-J.C., Y.-H.L. and H.-W.C.; Formal analysis, Y.-J.C.; Funding acquisition, Y.-H.H., I.-J.C., Y.-F.L., Y.-H.L. and H.-W.C.; Investigation, Y.-H.H., Y.-F.L. and H.-W.C.; Methodology, I.-J.C., Y.-J.C. and Y.-H.L.; Project administration, Y.-F.L.; Supervision, H.-W.C.; Author Contributions: Conceptualization, I-J.C.; Data curation, Y.-H.H., I-J.C., Y.-J.C., Y.-H.L. and H.-W.C.; Writing—original draft, Y.-H.H., Y.-H.L. and H.-W.C.; Writing—review and editing, Y.-H.L. and H.-W.C. All authors Formal analysis, Y.-J.C.; Funding acquisition, Y.-H.H., I-J.C., Y.F.L., Y.-H.L. and H.-W.C.; Investigation, Y.-H.H., Y.F.L. and H.-W.C.; Methodology, I-J.C., Y.-J.C. and Y.-H.L.; Project administration, Y.F.L.; Supervision, Funding: This study was supported by the Ministry of Science and Technology, Taiwan (MOST 106-2314-B-038-069-MY3, MOST 108-2314-B-039-061-MY3 and MOST 108-2314-B-038-044) and the Taipei Medical University-Shuang Ho Hospital (10H8T.-MWU.C-.S AHlHl a-0u1t)h. ors read and agreed to the published version of the manuscript. Funding Information: This study was supported by the Ministry of Science and Technology, Taiwan (MOST 106-2314-B-038-069-MY3, MOST 108-2314-B-039-061-MY3 and MOST 108-2314-B-038-044) and the Taipei Medical University-Shuang Ho Hospital (108TMU-SHH-01). Funding Information: Acknowledgments: Experiments and data analysis were performed in part through the use of the Medical Funding: This study was supported by the Ministry of Science and Technology, Taiwan (MOST Research Core Facilities Center, Office of Research & Development at China Medical University, Taichung, Taiwan. 106-2314-B-038-069-MY3, MOST 108-2314-B-039-061-MY3 and MOST 108-2314-B-038-044) and the Taipei Conflicts of Interest: The authors declare no conflict of interest. Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2020",
month = may,
doi = "10.3390/pharmaceutics12050434",
language = "English",
volume = "12",
journal = "Pharmaceutics",
issn = "1999-4923",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "5",
}