Inhibition of lysyl oxidase‑like 2 ameliorates folic acid‑induced renal tubulointerstitial fibrosis

Choi,Sung-Eun; Jeon,Nara; Choi,Hoon Young; Jeong,Hyeon Joo; Lim,Beom Jin

doi:10.3892/etm.2022.11585

Inhibition of lysyl oxidase‑like 2 ameliorates folic acid‑induced renal tubulointerstitial fibrosis

Authors:
- Sung-Eun Choi
- Nara Jeon
- Hoon Young Choi
- Hyeon Joo Jeong
- Beom Jin Lim
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Affiliations: Department of Pathology, CHA University, CHA Bundang Medical Center, Seongnam, Kyeonggi 13496, Republic of Korea, Department of Pathology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
Published online on: September 2, 2022 https://doi.org/10.3892/etm.2022.11585
Article Number: 648
Copyright: © Choi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Tubulointerstitial fibrosis is characterized by accumulation of the extracellular matrix in the interstitium. Lysyl oxidase‑like 2 (LOXL2), a member of the lysyl oxidase family, is known for promoting cancer metastasis, invasion and stromal fibrosis in various organs. Our previous study demonstrated expression of LOXL2 in kidney podocytes and tubular epithelial cells, and the association between elevated LOXL2 and tubulointerstitial fibrosis. The present study evaluated the effect of LOXL2 inhibition using an inhibitory monoclonal antibody (AB0023) on tubulointerstitial fibrosis in a folic acid‑induced tubulointerstitial fibrosis mouse model. The association of LOXL2 with epithelial‑mesenchymal transformation‑related molecules was also evaluated in vitro using HK‑2 cells. The present data demonstrated that AB0023 prevented the progression of tubulointerstitial fibrosis significantly, as determined by trichrome and picro‑sirius red staining, as well as the total collagen assay. The mean expression of phosphorylated Smad2 and Smad4 was lower in the AB0023‑treated group although it was not statistically significant. Following transforming growth factor‑β (TGF‑β) challenge, LOXL2‑deficient HK‑2 cells exhibited significantly lower expression of the mesenchymal markers vimentin and fibronectin than control HK‑2 cells. In conclusion, LOXL2 inhibition ameliorates renal fibrosis through the TGF‑β/Smad signalling pathway.

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