<p>Panax Notoginseng Ameliorates Podocyte EMT by Targeting the Wnt/β-Catenin Signaling Pathway in STZ-Induced Diabetic Rats</p>

Abstract

Introduction: Epithelial-mesenchymal transition (EMT) may contribute to podocyte dysfunction in diabetic nephropathy (DN). Aiming to identify novel therapeutic options, we investigated the protective effects of Panax notoginseng (PN) on podocyte EMT in diabetic rats and explored its mechanisms. Methods: Diabetes was induced in rats with streptozotocin (STZ) by intraperitoneal injection at 55 mg/kg. Diabetic rats were randomly divided into three groups, namely, diabetic rats, diabetic rats treated with beraprost sodium (BPS) at 0.6 mg/kg/d or PN at 0.4 g/kg/d p. o., for 12 weeks. Urinary albumin/creatinine ratio (ACR), biochemical parameters, renal histopathology, and podocyte morphological changes were evaluated. Protein expression of EMT markers (desmin, α-SMA, and nephrin) as well as components of the Wnt/β-catenin pathway (wnt1, β-catenin, and snail) was detected by immunohistochemistry and Western blot, respectively. Results: In diabetic rats, severe hyperglycemia and albuminuria were detected. Moreover, mesangial expansion and podocyte foot process effacement were found markedly increased in diabetic kidneys. Increased protein expression of wnt1, β-catenin, snail, desmin, and α-SMA, as well as decreased protein expression of nephrin was detected in diabetic kidneys. All these abnormalities found in DN rats were partially restored by PN treatment. Conclusion: PN ameliorated albuminuria and podocyte EMT in diabetic rats partly through inhibiting Wnt/β-catenin signaling pathway. These findings provide experimental arguments for a novel therapeutic option in DN.

Astragaloside II Ameliorated Podocyte Injury and Mitochondrial Dysfunction in Streptozotocin-Induced Diabetic Rats

“…Healthy 8-week-old male Sprague-Dawley rats weighing 200–250 g were housed under a constant 12 h light–dark cycle at a temperature between 21 and 23°C and allowed free access to food and water. Diabetes was induced in rats by a single intraperitoneal injection of STZ at 55 mg/kg, according to our previous study ( Xie et al, 2020 ). Seventy-two hours after intraperitoneal injection of STZ, the blood glucose level was measured from the tail vein, and rats with a blood glucose level above 16.7 mmol/L were considered as diabetic rats ( Xie et al, 2020 ).…”

“…Diabetes was induced in rats by a single intraperitoneal injection of STZ at 55 mg/kg, according to our previous study ( Xie et al, 2020 ). Seventy-two hours after intraperitoneal injection of STZ, the blood glucose level was measured from the tail vein, and rats with a blood glucose level above 16.7 mmol/L were considered as diabetic rats ( Xie et al, 2020 ). The diabetic rats were then randomly divided into four groups ( n = 7/each group): 1) STZ-induced diabetic rats (STZ), received an equal volume of olive oil; 2) diabetic rats treated with losartan at 10 mg·kg −1 ·d −1 ; 3) diabetic rats treated with low-concentration of AS II at 3.2 mg·kg −1 ·d −1 (ASIIL); 4) diabetic treated with high-concentration of AS II at 6.4 mg·kg −1 ·d −1 (ASIIH).…”

USP36-Mediated Deubiquitination of DOCK4 Contributes to the Diabetic Renal Tubular Epithelial Cell Injury via Wnt/β-Catenin Signaling Pathway

“…With this purpose, potential interactions with USP36 were speculated in string 1 (Figure 4A). Among these proteins, particularly interest is DOCK4, due to its function in activating Wnt/βcatenin signaling pathway, which is associated with renal fibrosis (Xie et al, 2020). First, we evidenced that USP36 physically interacts with DOCK4 by IP and in situ proximity ligation assay (in situ PLA) ( Figures 4B,C).…”

“…Previous studies demonstrated that DOCK4 is responsible for the degradation of β-catenin (Xie et al, 2020). Under this study, whether USP36 has an effect on EMT through DOCK4-dependent Wnt/β-catenin signaling pathway in TECs under high glucose condition has aroused our attention.…”

Antiepithelial-Mesenchymal Transition of Herbal Active Substance in Tumor Cells via Different Signaling

“…Panax notoginseng (PN) targets the Wnt/β-catenin signaling pathway in rats. By increasing the expression of Wnt1, β-catenin, and Snail, PN can upregulate the expression of desmin and α-SMA protein and reduce the expression of nephrin, thereby ameliorating podocyte EMT [70]. Emodin is extracted from Polygonum cuspidatum, rhubarb, and other rhizomes from a class of bioactive substances which possess anti-inflammatory, antioxidative, and other pharmacological activities.…”