Salidroside alleviates high glucose-induced oxidative stress and extracellular matrix accumulation in rat glomerular mesangial cells by the TXNIP-NLRP3 inflammasome pathway
Introduction
Diabetic nephropathy (DN) is the major cause of end stage renal disease and closely associated with the mortality rate of diabetic patients [1], [2]. It has been proved that DN is characterized by thickened tubular basal and glomerular membranes, mesangial cell proliferation and accumulation of extracellular matrix (ECM) [1], [3]. Growing evidences prove that DN is induced by various conditions, including glucose metabolism disorder, oxidative stress, inflammatory factors and cytokines [3].
Nod-like receptor protein 3 (NLRP3) inflammasome is a polyprotein complex which plays an important role in the process of inflammation [4]. The NLRP3 inflammasome consists of three inflammasome components, NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), and caspase-1 or caspase-5 [5]. It is crucial for DN that NLRP3 inflammasome detects the endogenous danger signals and activates the cytokines, and then stimulate the inflammatory reaction [6]. Moreover, the NLRP3 inflammasome is activated by oxidative stress, hyperglycaemia and growth factors in a variety of cell types in DN [6], [7].
Salidroside (SAL), 2-(4-hydroxyphenyl)-ethyl--d-glucopyranoside, is the major ingredient in Rhodiola rosea, which is a herbal plant and possesses protective effects against early nephropathy in diabetic rat [8]. It has been reported that SAL has broad pharmacological activities, such as antidiabetic, hepatoprotective, and antioxidative effects [9], [10], [11]. SAL also possesses beneficial effects on DN and affects the high-glucose (HG)-induced mesangial cell proliferation [12]. However, the effect of SAL on HG-induced DN in rat glomerular mesangial cells is still incompletely understood.
In the present study, the effect of SAL on HG-induced oxidative stress and ECM accumulation and the underlying mechanism was investigated. We found that SAL alleviated HG-induced oxidative stress and ECM accumulation in rat glomerular mesangial cells by the TXNIP-NLRP3 inflammasome pathway. The results indicated that SAL might be a useful agent for preventing the development and progression of DN.
Section snippets
Cell culture and treatment
Rat glomerular mesangial cell line HBZY-1 was purchased from KeyGen Biotechnology (Nanjing, China). Cells were cultured in Dulbecco's modified eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 100 U/ml penicillin and 100 mg/ml streptomycin in a humidified atmosphere of 5% CO2 at 37 °C. The HBZY-1 cells were stimulated with various concentrations of SAL (20 or 40 μM; Sigma, St. Louis, MO, USA) in the presence of normal glucose (NG, 5.5 mM), high glucose (HG, 30 mM) or
SAL inhibits HG-induced cell proliferation
It has been reported that HG induces cell proliferation in mesangial cells [13]. To evaluate the effect of SAL on HG-induced cell proliferation in HBZY-1 cells, CCK-8 assay was performed in this study. As shown in Fig. 1A and B, the cell proliferation was not altered by either normal glucose or mannitol. HG significantly induced cell proliferation of HBZY-1 cells. However, SAL (20 or 40 μM) treatment alleviated HG-induced cell proliferation (Fig. 1C).
SAL alleviates HG-induced oxidative stress
It is known that oxidative stress plays an
Discussion
It is known that HG concentrations affect many types of cells in the kidney including mesangial cells [14]. Previous studies reported that glucose induced oxidative stress in mesangial cells [14], [15], [18]. Glucose not only promotes generation of ROS but also attenuates the antioxidant. Besides, glucose exposure stimulates the increased accumulation of ECM protein in DN [14]. It has been demonstrated that HG concentration suppresses human mesangial cell proliferation and stimulates
Conflicts of interest
The authors declare that they have no competing interests.
Acknowledgements
This work was financially supported by Scientific and technological Key Project of Henan Province (No. 201003089).
References (25)
- et al.
Roles of the NLRP3 inflammasome in the pathogenesis of diabetic nephropathy
Pharmacol. Res.
(2016) - et al.
Nlrp3-inflammasome activation in non-myeloid-derived cells aggravates diabetic nephropathy
Kidney Int.
(2015) - et al.
Betulinic acid inhibits cell proliferation and fibronectin accumulation in rat glomerular mesangial cells cultured under high glucose condition
Biomed. Pharmacother.
(2016) - et al.
Glucose-induced oxidative stress in mesangial cells
Kidney Int.
(2002) - et al.
NLRs join TLRs as innate sensors of pathogens
Trends Immunol.
(2005) - et al.
Salidroside contributes to reducing blood pressure and alleviating cerebrovascular contractile activity in diabetic Goto-Kakizaki Rats by inhibition of L-type calcium channel in smooth muscle cells
BMC Pharmacol. Toxicol.
(2017) - et al.
Salidroside attenuates ventilation induced lung injury via SIRT1-dependent inhibition of NLRP3 inflammasome
Cell. Physiol. Biochem.
(2017) - et al.
Diabetic nephropathy: new risk factors and improvements in diagnosis
Rev. Diabet. Stud.
(2015) - et al.
Diabetic kidney disease: pathophysiology and therapeutic targets
J. Diabetes Res.
(2015) - et al.
Research progress in signalling pathway in diabetic nephropathy
Diabetes Metab. Res. Rev.
(2015)
Activation of Nod-like receptor protein 3 inflammasomes turns on podocyte injury and glomerular sclerosis in hyperhomocysteinemia
Hypertension
The NALP3 inflammasome is involved in the innate immune response to amyloid-beta
Nat. Immunol.
Cited by (0)
- 1
These authors contributed equally to this work.