Po‑Yu Huanga,b,†, Yi‑Hsien Hsiehc,d,†, Yi‑Hsuan Tingc, Chu‑Che Leee, Jen‑Pi Tsaia,b*
aDivision of Nephrology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan, bSchool of Medicine, Tzu Chi University, Hualien, Taiwan, cInstitute of Medicine, Chung Shan Medical University, Taichung, Taiwan, dDepartment of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan, eDepartment of Medicine Research, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
†Both authors contributed equally to this work.
Open Access funded by Buddhist Compassion Relief Tzu Chi Foundation
Abstract
Objectives: Ellagic acid (EA), a kind of polyphenol found in numerous fruits and vegetables, has anti‑inflammatory, anti‑apoptotic, anti‑oxidant, and anti‑fibrotic effects against a variety of diseases, but its role in mediating renal fibrogenesis remains unknown. Materials and Methods: We used an in vivo mouse unilateral ureteral obstruction (UUO) model and an in vitro model with HK‑2 cell lines treated with EA and transforming growth factor β1 (TGF‑β1). The expression of epithelial‑to‑mesenchymal transition (EMT)‑related proteins of UUO mice was examined using immunohistochemical staining. Liver function and renal function were evaluated using biochemical testing. Western blot analysis was used to determine the proteins related to EMT, and MTT assay was used to determine cell viability. Results: In UUO mice fed EA, both microscopical examination with immunohistochemical staining and western blotting protein analysis showed reduced expression of fibrotic (α‑SMA, fibronectin, and collagen I)‑ and EMT (vimentin and N‑cadherin)‑related proteins, compared with sham control. In HK‑2 cells treated with TGF‑β1, EA decreased motility as well as expression of α‑SMA, collagen‑I, fibronectin, N‑cadherin, and vimentin. Conclusion: EA reduced the progression of the morphological transformations and concomitantly suppressed the expression of fibrotic‑ and EMT‑related proteins in vitro and in vivo. These findings improved our understanding of the role of EA in suppressing renal fibrogenesis and demonstrated the promising role EA may play in the management of chronic kidney disease.
Keywords: Ellagic acid, Epithelial‑to‑mesenchymal transition, Transforming growth factor β1, Unilateral ureteral obstruction
