Nobiletin suppresses high‐glucose–induced inflammation and ECM accumulation in human mesangial cells through STAT3/NF‐κB pathway

Abstract

Diabetic nephropathy (DN) is a complication of chronic diabetes and the main cause of end-stage renal disease all over the world. Inflammation and extracellular matrix (ECM) accumulation play important roles in the pathogenesis of DN.Evidence suggested that nobiletin acts anti-inflammatory role and plays a critical role in diabetes; however, its role in DN remains unclear. In the current study, we promulgated the nobiletin involved in high-glucose-induced glomerular mesangial cell inflammation and ECM accumulation. Nobiletin treatment significantly abrogated high-glucose-induced glomerular mesangial cell proliferation. Nobiletin treatment markedly suppressed inflammation cytokine secretion, including interleukin (IL)-1β, IL-6, tumor necrosis factor α, and monocyte chemoattractant protein 1 in high-glucose-induced glomerular mesangial cell. Also, exposed nobiletin to high-glucose-induced glomerular mesangial cell considerably reduced ECM accumulation through inhibited ECM-associated protein type 4 collagen and fibronectin expression. Furthermore, nobiletin treatment abolished nuclear factor κB (NF-κB) pathway activation through signal transducer and activator of transcription 3 (STAT3) inhibition. Overexpression STAT3 reversed the effects of nobiletin on high-glucose-induced glomerular mesangial cell proliferation, inflammation, ECM accumulation, and NF-κB pathway activation. Hence, our results suggest that nobiletin play roles in high-glucose-induced glomerular mesangial cells through inhibiting inflammation and ECM accumulation, and the STAT3/NF-κB pathway was involved in the function of nobiletin. K E Y W O R D S diabetic nephropathy, extracellular matrix accumulation, inflammation, nuclear factor κB pathway, nobiletin, signal transducer and activator of transcription 3

Tim-3 aggravates podocyte injury in diabetic nephropathy by promoting macrophage activation via the NF-κB/TNF-α pathway

“…Treatment of diabetic rats with NF-κB inhibitors for 4 weeks led to reduced renal macrophage infiltration, decreased production of inflammatory cytokines, and consequently reversed renal dysfunction [11]. Although NF-κB inhibitors are not currently used in the treatment of renal diseases, many drugs applied in clinical have been shown to suppress NF-κB signaling and decrease proteinuria [12], [13]. Therefore, it is necessary to explore new factors that might be responsible for regulating renal inflammation, especially the NF-κB signaling pathway in renal macrophages, which may provide novel therapies to treat renal inflammation in the development of DN.…”

Knockdown of ANGPTL-4 inhibits inflammatory response and extracellular matrix accumulation in glomerular mesangial cells cultured under high glucose condition

“…In addition, NF-jB is an important transcriptional factor that is involved in multiple cellular responses to stimuli [19]. Several lines of evidence support the fundamental role of the transcriptional factor NF-jB in the mesangial cells during the progress of DN [20][21][22]. The increased AGEs interact through the cellular receptors to favor activation of the transcription factor NF-jB and the protein kinase C system, leading to the appearance of inflammation, growth, and augmentation of synthesis of the ECM [15].…”

LncRNA KCNQ1OT1 affects cell proliferation, apoptosis and fibrosis through regulating miR-18b-5p/SORBS2 axis and NF-ĸB pathway in diabetic nephropathy

“…It is well known that NF-κB signaling pathway plays an important role in disease progression. A previous study manifested that STAT3/NF-κB pathway facilitated inflammation and ECM accumulation in high glucose-induced human mesangial cells [ 34 ]. NF-κB and STAT3 have been revealed to regulate inflammation and cell adhesion [ 35 ].…”