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

Abstract

Abstract. The aim of the present study was to investigate the effect of Yi Qi Qing Re Gao-containing serum (YQ-S) on rat mesangial cell (MC) proliferation and to investigate the underlying mechanism. MCs were divided into the control, lipopolysaccharide (LPS)-stimulated, YQ-S and fosinopril-containing serum (For-S) groups, and cultured for 48 h. An MTT assay was used to evaluate the proliferation of MCs. In addition, reverse transcription-quantitative polymerase chain reaction and western blot analysis were conducted to detect the expression levels of Wnt4, β-catenin and transforming growth factor (TGF)-β1 in MCs. The results indicated that YQ-S inhibited LPS-induced MC proliferation. The Wnt4 and TGF-β1 mRNA expression levels were reduced in the YQ-S group (P<0.01 or P<0.05). Furthermore, the Wnt4, β-catenin and TGF-β1 protein expression levels were suppressed in the YQ-S group (P<0.01 or P<0.05). Therefore, YQ-S appears to inhibit MC proliferation, and its mechanism may involve the inhibition of the Wnt signaling pathway and downregulation of TGF-β1 expression. IntroductionChronic kidney disease (CKD) is a major challenge for global public health care, due to its irreversible progression, low awareness and high cost (1). Due to the progressive aging of the general population, and the emerging epidemic of obesity and diabetes, CKD is now one of the three leading causes of mortality worldwide (1,2). Studies regarding the pathogenesis of CKD have predominantly focused on glomerular sclerosis and interstitial fibrosis, with disturbance of extracellular matrix (ECM) homeostasis (i.e. synthesis and degradation) a common factor (3). Mesangial lesions, caused by mesangial cell (MC) proliferation and accumulation of ECM, are universal morphological manifestations of renal diseases that involve the mesangium. There are numerous growth factors, cytokines and signaling pathways that are involved in the process of mesangial fibrosis, among which transforming growth factor-β1 (TGF-β1) is the most versatile, with functions in cell growth, apoptosis, proliferation, and ECM production (4). TGF-β1 is able to affect MC proliferation, and stimulate the synthesis and inhibit the degradation of ECM in an autocrine or paracrine manner, leading to relentless progression of glomerular sclerosis (5).The Wnt signaling pathway is a key regulator of embryonic development, tissue homeostasis, cell apoptosis, proliferation and differentiation (6-8). There are 19 known Wnts, which mediate at least three divergent signaling pathways: The β-catenin dependent pathway (canonical Wnt pathway), the Ca 2+ -pathway, and the planar cell polarity-pathway; the latter two pathways are also known as non-canonical Wnt pathways. In the canonical Wnt pathway, Wnt proteins bind to a receptor complex formed by Frizzled and low-density lipoprotein receptor-related protein 5 or 6, which leads to disassembly of the β-catenin destruction complex, which is composed of axin, adenomatous polyposis coli protein, and glycogen synthase kinase-3β (8). Disassembly of the...

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