Protective effects of Schisandrin on high glucose-induced changes of RhoA and eNOS activity in human umbilical vein endothelial cells.

Schisandrin, derived from the Chinese medicinal herb Schisandra chinensis, has been found to confer protective effects on circulation systems. But the underlying molecular mechanisms remain unclear. The aim of this study was to investigate the effects of a high level of glucose on RhoA and eNOS activity in human umbilical vein endothelial cells(HUVECs) and how Schisandrin plays a role in mediating these effects.

TLR2 Plays a Critical Role in HMGB1-Induced Glomeruli Cell Proliferation Through the FoxO1 Signaling Pathway in Lupus Nephritis.

The objective of this study was to examine the role and possible mechanisms of toll-like receptor 2 (TLR2) in high-mobility group box chromosomal protein 1 (HMGB1)-induced mouse mesangial cell (MMC) proliferation and glomeruli proliferation of MRL/Fas(lpr) mice. First, the expression of proliferating cell nuclear antigen (PCNA), TLR2 and Forkhead box protein O1 (FoxO1) messenger RNA (mRNA) and protein in the glomeruli of MRL/Fas(lpr) mice was quantified, and the correlation with cell proliferation of glomeruli was analyzed. Then, lipopolysaccharide (LPS), TLR2 neutralization antibody, and small hairpin TLR2 (shTLR2) were used to confirm the role of TLR2 in HMGB1-induced MMC proliferation.

The PTEN/PI3K/Akt signaling pathway mediates HMGB1-induced cell proliferation by regulating the NF-κB/cyclin D1 pathway in mouse mesangial cells.

Our previous experiment confirmed that high-mobility group box chromosomal protein 1 (HMGB1) was involved in the pathogenesis of Lupus nephritis (LN) by upregulating the proliferation of the mouse mesangial cell line (MMC) through the cyclin D1/CDK4/p16 system, but the precise mechanism is still unknown. Therefore, in the present study, we demonstrated that HMGB1 induced the proliferation of MMC cells in a time- and concentration-dependent manner, downregulated phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression, increased the level of Akt serine 473 phosphorylation, and induced p65 subunit nuclear translocation. The overexpression of PTEN prevented the upregulation of HMGB1-induced proliferation by blocking the activation of Akt.

Interplay between the Notch and PI3K/Akt pathways in high glucose-induced podocyte apoptosis.

Podocyte apoptosis contributes to the pathogenesis of diabetic nephropathy (DN). However, the mechanisms that mediate high glucose (HG)-induced podocyte apoptosis remain poorly understood. Conditionally immortalized mouse podocytes were cultured in HG medium.

[HMGB1/SREBP-1 mediated IFN-gamma-induced lipid deposition in mouse mesangial cells].

Objective: To explore the possible mechanism of lipid deposition induced by interferon-gamma (IFN-gamma).

Methods: The mouse mesangial cells (MMC) were randomly divided into control group, stimulation group, stimulation + control vector group (sh-HMGB1) and stimulation+ specific sh-vector group (sh-SREBP-1). RT-PCR was used to detect the expression of HMGB1, SREBP-1 and fatty acid synthetase (FAS) mRNA; the protein expression was determined by Western blot.

[The relationship between endoplasmic reticulum stress and its particular apoptosis way caspase-12 and apoptosis in renal cortex of diabetic rats].

Objective: To investigate the expressions of 78-kDa glucose-regulated protein (GRP78) and Caspase-12 and their relationship with apoptosis in renal cortex of diabetic rats.

Methods: Uninephrectomized Wistar rats were used to induce diabetes by intraperitoneal injection of Streptozotocin (STZ 65 mg/kg). After 8 weeks, the expression and distribution of GRP78, Caspase-12, proliferating cell nuclear antigen (PCNA) were examined by immunohistochemistry.

High-fat diet causes increased serum insulin and glucose which synergistically lead to renal tubular lipid deposition and extracellular matrix accumulation.

Renal tubular lipid accumulation is associated with renal injury in the metabolic syndrome, but its mechanisms are not fully elucidated. The purpose of the present study was to investigate the exact mechanism of renal tubular lipid accumulation in the diet-induced metabolic syndrome. The in vivo experiments showed that a high-fat diet induced hyperglycaemia, hyperinsulinaemia and hypertriacylglycerolaemia, subsequent increases in sterol regulatory element binding protein-1 (SREBP-1) and transforming growth factor-β1 (TGF-β1), lipid droplet deposit in renal tubular cells and interstitial extracellular matrix accumulation in Wistar rats.

[The effect of Janus kinase 2 inhibitor AG490 on renal tubular epithelial-myofibroblast transdifferentiation induced by interleukin-1β].

Objective: To investigate the effect of AG490, a Janus kinase 2 inhibitor, on epithelial-myofibroblast transdifferentiation induced by interleukin-1β (IL-1β).

Methods: Cultured human renal tubular epithelial cell line (HKCs) were divided into three groups: blank control group, IL-1β (5 ng/ml) group and AG490 group (IL-1β 5 ng/ml+AG490 10 μmol/L). The cells in all groups were collected at 24, 48, 72 hours after intervention.

High mobility group box 1 induces synoviocyte proliferation in rheumatoid arthritis by activating the signal transducer and activator transcription signal pathway.

Recently, it was discovered that high mobility group box chromosomal protein 1 (HMGB1) acts as a potent pro-inflammatory cytokine that is released into the extracellular milieu. Signal transducer and activator of transcription (STAT) proteins play an important role in cytokine signaling. Some investigators have reported preferential activation of STAT1, and others have reported preferential activation of STAT3 in response to endogenous interleukin-6 (IL-6) in patients with rheumatoid arthritis.

The regulatory effect of the p38 signaling pathway on valdecoxib-induced apoptosis of the Eca109 cell line.

Valdecoxib is a second generation selective COX-2 inhibitor that can induce cell apoptosis in a variety of cell types, but its precise regulatory mechanism is unknown. Apoptosis of Eca109 cells and p38 mRNA expression were investigted. The expression of p-p38MAPK, Fas and FasL proteins were detected by immunohistochemical staining and FCM.

[Effects of fluvastatin on the expression of Janus kinase 2/signal transducers and activators of transcription (JAK/STAT) in glomerular mesangial cells under high concentration of glucose].

Objective: To investigate the effects of fluvastatin on activation of Janus kinase 2 (JAK2) and signal transducers and activators of transcription 1, 3 (STAT1, 3) in glomerular mesangial cells(GMCs) under high concentration of glucose.

Methods: Rat GMCs were cultured in vitro, and they were treated with glucose and fluvastatin respectively. Tyrosine phosphorylation of JAK2 (p-JAK2) expression was detected by immunoprecipitation and Western blotting analysis.

[Tubular epithelial-myofibroblast transdifferentiation and expressions of hepatocyte growth factor and Smad7 in renal tissues of rat with experimental diabetes].

Objective: To investigate the relationship of tubular epithelial-myofibroblast transdifferentiation and the expressions of hepatocyte growth factor (HGF) and Smad7, and to elucidate the role of HGF and Smad7 in diabetic nephropathy.

Methods: Diabetes was induced in male Wistar rats with right nephrectomy and streptozotocin (STZ) administration. The expressions of cytokeratin 18 (CK18), alpha-smooth muscle actin (alpha-SMA), HGF and Smad7 were assayed with immunohistochemistry.

[Effect of losartan on expression of Janus kinase 2 and signal transducer and activator of transcription 3 in glomeruli of diabetic rats].

Objective: To investigate the effects of losartan on Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 in glomeruli of diabetic rats.

Methods: Sixty Wistar male rats were randomly divided into control group (n=20), diabetes group (n=20), and losartan treatment group (n=20). Diabetes was induced by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg).

[Protective effects of Lovastatin on early diabetic renal tissue and the possible mechanism].

Objective: To investigate the protective effects of Lovastatin on renal function in experimental diabetic nephropathy in rats. and the function of cAMP-responsive element binding protein (CREB1) in this duration.

Methods: Diabetes was induced in male Wistar rats by intrapetitoneal injection of STZ (65 mg/kg).

[Effects of lovastatin on renal function and expression of phosphorylating-p38 mitogen-activated protein kinase in experimental diabetic nephropathy in rats].

Objective: To investigate the effects of lovastatin on renal function, activity and expression of the p38 mitogen-activated protein kinase (MAPK) and cAMP responsive element-binding protein (CREB) in experimental diabetic nephropathy in rats.

Methods: Eighteen uninephrectomized male Wistar rats were randomly divided into three groups: control (n=6), diabetic (n=6) and lovastatin treatment group (n=6). Diabetes was induced by intraperitoneal injection of STZ (65 mg/kg).

[Effects of puerarin on renal function, expressions of MMP-2 and TIMP-2 in diabetic rats].

Aim: To investigate the effect of puerarin on expressions of MMP-2 and TIMP-2 in the kidney of diabetic rats.

Methods: Uninephrectomized male Wistar rats were used to induce diabetes by intraperitoneal injection of streptozocin (65 mg x kg(-1)). Puerarin was given daily by intraperitoneal injection from the third day of induction of diabetes for 16 weeks.