Yi Qi Qing Re Gao Attenuates Podocyte Injury and Inhibits Vascular Endothelial Growth Factor Overexpression in Puromycin Aminonucleoside Rat Model

Abstract

Proteinuria is the hallmark of chronic kidney disease. Podocyte damage underlies the formation of proteinuria, and vascular endothelial growth factor (VEGF) functions as an autocrine/paracrine regulator. Yi Qi Qing Re Gao (YQQRG) has been used to treat proteinuria for more than two decades. The objective of this study was to investigate the protective effect and possible mechanisms of YQQRG on puromycin aminonucleoside (PAN) rat model. Eighty male Sprague-Dawley rats were randomized into sham group, PAN group, PAN + YQQRG group, and PAN + fosinopril group. Treatments were started 7 days before induction of nephrosis (a single intravenous injection of 40 mg/kg PAN) until day 15. 24 h urinary samples were collected on days 5, 9, and 14. The animals were sacrificed on days 3, 10, and 15, respectively. Blood samples and renal tissues were obtained for detection of biochemical and molecular biological parameters. YQQRG significantly reduced proteinuria, elevated serum albumin, and alleviated renal pathological lesions. YQQRG inhibited VEGF-A, nephrin, podocin, and CD2AP mRNA expression and elevated nephrin, podocin, and CD2AP protein levels starting on day 3. In conclusion, YQQRG attenuates podocyte injury in the rat PAN model through downregulation of VEGF-A and restoration of nephrin, podocin, and CD2AP protein expression.

Yi Qi Qing Re Gao-containing serum inhibits lipopolysaccharide-induced rat mesangial cell proliferation by suppressing the Wnt pathway and TGF-β1 expression

“…The effectiveness of YQ for treating chronic nephritis has been indicated by previous studies in animal models and patients (19)(20)(21). The pharmacological mechanisms underlying the effects of this mixture have yet to be elucidated.…”

“…Furthermore, a previous animal study in an adriamycin rat model suggested that YQ may be able to reduce glomerular mesangial collagen type Ⅳ, fibronectin and laminin content (20). Our recent study revealed that YQ was able to attenuate podocyte injury and inhibit vascular endothelial growth factor overexpression in a puromycin aminonucleoside rat model (21). However, the mechanisms underlying the effects of YQ on MC proliferation and glomerular sclerosis remain to be elucidated.…”

Yi Qi Qing Re Gao formula ameliorates puromycin aminonucleoside-induced nephrosis by suppressing inflammation and apoptosis

“…Podocyte apoptosis is largely involved in PAN-induced nephrosis and the progression of focal segmental glomerulosclerosis [ 20 ]; PAN causes apoptosis in cultured podocytes [ 21 ]. In our previous study, we found that pretreatment with YQQRG inhibited reduction of podocyte-specific molecular nephrin, podocin and CD-2AP in the PAN model [ 8 ]. In this study, we found significant cell apoptosis in the podocytes and tubules, which treatment with YQQRG could reduce.…”

“…Treatment with serum containing YQQRG, which was collected from YQQRG treated healthy Wistar rats, ameliorated lipopolysaccharide-stimulated rat mesangial cell proliferation in vitro (L Yang, et al unpublished data). Another study found that pretreatment with YQQRG could protect the filtration barrier from PAN-induced architectural damage [ 8 ]. Since lipopolysaccharide is a powerful stimulus for inflammation, and apoptosis is frequently involved in architectural damage, we hypothesize the renoprotective effects of YQQRG may due to its anti-inflammatory and anti-apoptotic actions.…”

Traditional Chinese Medicine in the Treatment of Chronic Kidney Diseases: Theories, Applications, and Mechanisms

“…Animal experiments have shown that the formula inhibits the expression levels of inflammatory factors such as TNF-α, TNFR1, IL-1β, and MCP-1 in renal tubulointerstitium, downregulates the expression level of caspase-3 in the renal tissues, and upregulates the expression level of Bcl-2 to exert an antiapoptotic effect ( Wen et al, 2015 ). In maintaining the glomerular filtration barrier, YQQRG could upregulate the expressions of podocyte-related proteins such as nephrin, podocin, and CD2AP in kidney tissues of rats with PAN nephropathy and inhibit their mRNA level in feedback ( Zhan et al, 2014 ). Moreover, the main molecular chaperones of endoplasmic reticulum stress, such as glucose-regulated protein 78 (GRP78) and GRP94, and cytoskeletal regulatory proteins, such as α-actin-4, synaptopodin, desmin, and uPAR, were all inhibited by YQQRG ( Yang et al, 2016a ).…”