Fu-Fang-Jin-Qian-Cao herbal granules protect against the calcium oxalate-induced renal EMT by inhibiting the TGF-β/smad pathway

• Published in: Pharmaceutical biology 2020-01, Vol.58 (1), p.1124-1131
• Main Authors: Liu, Wen-Rui, Lu, Hong-Tao, Zhao, Ting-Ting, Ding, Jia-Rong, Si, Ya-Chen, Chen, Wei, Hou, Jie-Bin, Gao, Song-Yan, Dong, Xin, Yu, Bing, Guo, Zhi-Yong, Lu, Jian-Rao
• Format: Article
• Language: English
• Subjects: Actin; Calcium oxalate; Collagen (type II); Cytokeratin; E-cadherin; Fibrosis; Herbal medicine; Kidney stones; Kidneys; Mesenchyme; Nephrolithiasis; Oxalate crystals; Oxalic acid; Public health; renal fibrosis; Smad protein; Smooth muscle; Traditional Chinese medicine; Transforming growth factor-b; Vimentin; Western blotting
• ISSN: 1388-0209; 1744-5116
• DOI: 10.1080/13880209.2020.1844241

Nephrolithiasis is a major public health problem worldwide and Fu-Fang-Jin-Qian-Cao granules (FFJQC) is a traditional Chinese herbal formula that is used to treat nephrolithiasis. The main component of nephrolithiasis is calcium oxalate (CaOx) and the epithelial-mesenchymal transition (EMT) shown to play a crucial role in CaOx-induced kidney injury. However, the mechanism underlying the therapeutic effect of FFJQC on the CaOx-induced renal EMT is unknown. This study explores the therapeutic benefits and mechanism of FFJQC in oxalate-induced kidney injury. 60 male C57BL/6 mice were used in this experiment and divided into 6 groups. A mouse kidney stone model was created by intraperitoneal injection of glyoxylate at a dose of 100 mg/kg for 6 days. The standardized FFJQC was used to treat mouse crystal kidney injury by gavage at 1.35 and 2.7 g/kg, respectively. Western blotting and immunostaining for E-cadherin, cytokeratin 18 (CK18), vimentin, smooth muscle α-actin (α-SMA) and transforming growth factor β (TGF-β)/Smad pathway were conducted on renal tissues. Following CaOx-induced kidney injury, the levels of E-cadherin and CK18 in kidney decreased, while vimentin and α-SMA levels increased. The FFJQC treatment increased the levels of E-cadherin and CK18 and decreased vimentin and α-SMA levels in varying degrees. What's more, the FFJQC reduced the expression of CaOx-induced fibrosis marker collagen II. FFJQC alleviated the CaOx-induced renal EMT and fibrosis by regulating TGF-β/smad pathway. Therefore, the FFJQC is an important traditional Chinese medicine for the treatment of CaOx-induced renal injury and fibrosis.