Renal fibrosis is a crucial pathological phenomenon of chronic kidney disease (CKD) that contributes to the progressive loss of renal function. Monocarboxylate transporter 1 (MCT1) plays an important role in clear cell renal cell carcinoma; however, the role of the MCT1 inhibitor alpha-cyano-4-hydroxycinnamic acid (α-CHCA) in renal fibrosis remains unclear. In this study, we evaluated the role of α-CHCA, an MCT1 inhibitor, in treating renal fibrosis associated with CKD. We used α-CHCA in a CKD mouse model of unilateral ureteral obstruction (UUO), and mouse proximal tubular epithelial cells (mPTCs) stimulated by transforming growth factor-β1 (TGF-β1). In vivo, administration of α-CHCA improved tubulointerstitial fibrosis, which was consistent with the reduced expression of collagen I/III, fibronectin (FN1), and α-smooth muscle actin (α-SMA) in the kidneys of UUO mice. Similarly, the overexpression of inflammatory factors in UUO kidneys decreased in response to α-CHCA treatment. In vitro, α-CHCA pretreatment inhibited the induction of collagen I/III, FN1, and α-SMA production in mPTCs treated with TGF-β1. Collectively, these findings indicate that α-CHCA may play a therapeutic role in renal fibrosis associated with CKD by inhibiting collagen deposition and subsequent fibrosis and inflammation.

Highlights

• Chronic kidney disease (CKD) mice have increased MCT1 expression.

• α-CHCA, a MCT1 inhibitor, alleviates renal fibrosis in CKD mice.

• α-CHCA improves the inflammation in CKD mice.

• α-CHCA inhibits TGF-β1-induced extracellular matrix secretion of proximal tubular epithelial cells.

肾纤维化是慢性肾脏病（CKD）的重要病理现象，导致肾功能进行性丧失。单羧酸转运蛋白 1 (MCT1) 在透明细胞肾细胞癌中发挥重要作用；然而，MCT1抑制剂α-氰基-4-羟基肉桂酸（α-CHCA）在肾纤维化中的作用仍不清楚。在这项研究中，我们评估了 α-CHCA（一种 MCT1 抑制剂）在治疗 CKD 相关肾纤维化中的作用。我们在单侧输尿管梗阻 (UUO) 的 CKD 小鼠模型中使用 α-CHCA，并通过转化生长因子-β1 (TGF-β1) 刺激小鼠近端肾小管上皮细胞 (mPTC)。在体内，α-CHCA 的施用改善了肾小管间质纤维化，这与胶原蛋白 I/III、纤连蛋白 (FN1)、UUO 小鼠肾脏中的 α-平滑肌肌动蛋白 (α-SMA)。同样，UUO 肾脏中炎症因子的过度表达因 α-CHCA 治疗而减少。在体外，α-CHCA 预处理抑制了用 TGF-β1 处理的 mPTC 中胶原蛋白 I/III、FN1 和 α-SMA 的诱导。总的来说，这些发现表明 α-CHCA 可能通过抑制胶原蛋白沉积以及随后的纤维化和炎症，在与 CKD 相关的肾纤维化中发挥治疗作用。

强调

• 慢性肾病 (CKD) 小鼠的 MCT1 表达增加。

• α-CHCA 是一种 MCT1 抑制剂，可减轻 CKD 小鼠的肾纤维化。

• α-CHCA 改善 CKD 小鼠的炎症。

• α-CHCA 抑制 TGF-β1 诱导的近端肾小管上皮细胞的细胞外基质分泌。