Verbascoside and isoverbascoside ameliorate transforming growth factor β1-induced collagen expression by lung fibroblasts through Smad/non-Smad signaling pathways.

Aims: Pulmonary fibrosis (PF) is a chronic, irreversible, and debilitating lung disease that typically leads to respiratory failure, and is a major cause of morbidity and mortality. Few drugs are effective for the treatment of patients with PF or for reducing the rate of disease progression.

Main Methods: Transforming growth factor-β1 (TGF-β1) is a profibrotic cytokine that signals through Smad and non-Smad pathways.

Angiotensin-converting enzyme inhibitors attenuated advanced glycation end products-induced renal tubular hypertrophy via enhancing nitric oxide signaling.

Advanced glycation end products (AGE) and angiotensin II were closely correlated with the progression of diabetic nephopathy (DN). Nitric oxide (NO) is a protective mediator of renal tubular hypertrophy in DN. Here, we examined the molecular mechanisms of angiotensin-converting enzyme inhibitor (ACEI) and NO signaling responsible for diminishing AGE-induced renal tubular hypertrophy.

Effect of osthole on advanced glycation end products-induced renal tubular hypertrophy and role of klotho in its mechanism of action.

Background: Osthole has been widely reported to have pharmacological activities such as anti-cancer, anti-inflammation and anti-hyperlipidemic effects. Klotho was identified as an anti-senescence protein in a variety of tissues. Loss of klotho has been associated with chronic kidney disease.

Effects of probucol on cell proliferation in human ovarian cancer cells.

Probucol is considered to be an important agent in promoting anti-oxidative action and protecting against tissue injury. However, little is known about the effects of probucol on the progression of ovarian carcinoma. The aim of this study was to investigate the effects of probucol on cellular proliferation in human ovarian cancer cells (PA-1 and SKOV-3) and explore the anti-proliferative mechanism of probucol in these cells.

Cinnamaldehyde and nitric oxide attenuate advanced glycation end products-induced the Jak/STAT signaling in human renal tubular cells.

Cinnamaldehyde is a major and a bioactive compound isolated from the leaves of Cinnamomum osmophloeum kaneh. It possesses anti-diabetic properties in vitro and in vivo and has anti-inflammatory and anti-cancer effects. To explore whether cinnamaldehyde was linked to altered advanced glycation end products (AGE)-mediated diabetic nephropathy, the molecular mechanisms of cinnamaldehyde responsible for inhibition of AGE-reduced nitric oxide (NO) bioactivity in human renal proximal tubular cells were examined.

Klotho attenuates high glucose-induced fibronectin and cell hypertrophy via the ERK1/2-p38 kinase signaling pathway in renal interstitial fibroblasts.

Although exogenous klotho attenuates renal fibrosis, it is not known if exogenous klotho attenuates diabetic nephropathy (DN). Thus, we studied the anti-fibrotic mechanisms of klotho in terms of transforming growth factor-β (TGF-β) and signaling pathways in high glucose (HG, 30 mM)-cultured renal interstitial fibroblast (NRK-49F) cells. We found that HG increased klotho mRNA and protein expression.

Ubiquitin C-terminal hydrolase-L5 is required for high glucose-induced transforming growth factor-β receptor I expression and hypertrophy in mesangial cells.

Transforming growth factor-β (TGF-β) is pivotal in the pathogenesis of diabetic nephropathy. Type 1 TGF-β receptor (TGF-βR1) is degraded by Smad7-dependent ubiquitination-proteasomal pathway, which is deubiquitinated by ubiquitin C-terminal hydrolase-L5 (UCHL5). Therefore, we studied the role of UCHL5 in high glucose (27.

Advanced glycation end products-mediated hypertrophy is negatively regulated by tetrahydrobiopterin in renal tubular cells.

Diabetic nephropathy (DN) is the most common cause of end-stage renal disease worldwide. The accumulation of advanced glycation end products (AGE) is a key mediator of renal tubular hypertrophy in DN. Elimination of tetrahydrobiopterin (BH(4)) and nitric oxide (NO) bioavailability may contribute to the aggravation of DN.

The role of IL-7 in renal proximal tubule epithelial cells fibrosis.

Background: Hyperglycemia is the most important risk factor in the progression of renal fibrosis in diabetic kidney. Based on previous studies, interleukin-7 (IL-7) may exert antifibrotic activities in pulmonary fibrosis model. However, the role of IL-7 in the pathogenesis of renal tubulointerstitial fibrosis remains unclear.

Effect of Lactobacillus reuteri GMNL-263 treatment on renal fibrosis in diabetic rats.

Hyperglycemia is the most important factor in the progression of renal fibrosis in diabetic kidney. Prevention and treatment of renal fibrosis may improve diabetic nephropathy. To explore whether probiotic Lactobacillus reuteri GMNL-263 treatment was linked to altered hyperglycemia-mediated renal fibrosis in diabetic kidney, the mechanisms of L.

Cinnamaldehyde impairs high glucose-induced hypertrophy in renal interstitial fibroblasts.

Cinnamaldehyde is a major and a bioactive compound isolated from the leaves of Cinnamomum osmophloeum kaneh. To explore whether cinnamaldehyde was linked to altered high glucose (HG)-mediated renal tubulointerstitial fibrosis in diabetic nephropathy (DN), the molecular mechanisms of cinnamaldehyde responsible for inhibition of HG-induced hypertrophy in renal interstitial fibroblasts were examined. We found that cinnamaldehyde caused inhibition of HG-induced cellular mitogenesis rather than cell death by either necrosis or apoptosis.

Advanced glycation end-products activate extracellular signal-regulated kinase via the oxidative stress-EGF receptor pathway in renal fibroblasts.

Advanced glycation end-products (AGEs), epidermal growth factor receptor (EGFR), reactive oxygen species (ROS), and extracellular signal-regulated kinases (ERK) are implicated in diabetic nephropathy (DN). Therefore, we asked if AGEs-induced ERK protein phosphorylation and mitogenesis are dependent on the receptor for AGEs (RAGE)-ROS-EGFR pathway in normal rat kidney interstitial fibroblast (NRK-49F) cells. We found that AGEs (100 microg/ml) activated EGFR and ERK1/2, which was attenuated by RAGE short-hairpin RNA (shRNA).

Antimetastatic potential of fisetin involves inactivation of the PI3K/Akt and JNK signaling pathways with downregulation of MMP-2/9 expressions in prostate cancer PC-3 cells.

Fisetin (3,3',4',7-tetrahydroxyflavone), a naturally occurring flavonoid, has been reported to possess some anti-cancer and anti-inflammation capabilities. In this study, fisetin has exhibited inhibitory effects on the adhesion, migration, and invasion ability of a highly metastatic PC-3 cells under non-cytotoxic concentrations. Gelatin zymography assay showed that fisetin inhibited the matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) activities.

Effects of nitric oxide and antioxidants on advanced glycation end products-induced hypertrophic growth in human renal tubular cells.

The accumulation of advanced glycation end products (AGE) is a key mediator of renal tubular hypertrophy in diabetic nephropathy (DN). Reactive oxygen species and nitric oxide (NO) were involved in the progression of DN. In this study, the molecular mechanisms of NO and antioxidants responsible for inhibition of AGE-induced renal tubular hypertrophy were examined.

Effect of taurine on advanced glycation end products-induced hypertrophy in renal tubular epithelial cells.

Mounting evidence indicates that advanced glycation end products (AGE) play a major role in the development of diabetic nephropathy (DN). Taurine is a well documented antioxidant agent. To explore whether taurine was linked to altered AGE-mediated renal tubulointerstitial fibrosis in DN, we examined the molecular mechanisms of taurine responsible for inhibition of AGE-induced hypertrophy in renal tubular epithelial cells.

Safflower extract: a novel renal fibrosis antagonist that functions by suppressing autocrine TGF-beta.

Progressive renal disease is characterized by the accumulation of extracellular matrix proteins in the renal interstitium. Hence, developing agents that antagonize fibrogenic signals is a critical issue facing researchers. The present study investigated the blood-circulation-promoting Chinese herb, safflower, on fibrosis status in NRK-49F cells, a normal rat kidney interstitial fibroblast, to evaluate the underlying signal transduction mechanism of transforming growth factor-beta (TGF-beta), a potent fibrogenic growth factor.

Arecoline-induced growth arrest and p21WAF1 expression are dependent on p53 in rat hepatocytes.

Betel-quid use is associated with the risk of liver cirrhosis and hepatocellular carcinoma and arecoline, the major alkaloid of betel-quid, is hepatotoxic in mice. Therefore, we studied the cytotoxic and genotoxic effects of arecoline in normal rat hepatocytes (Clone-9 cells). Arecoline dose-dependently (0.

High glucose decreases endothelial cell proliferation via the extracellular signal regulated kinase/p15(INK4b) pathway.

High glucose inhibits endothelial cell proliferation. Thus, we studied cyclin-dependent kinase inhibitor p15(INK4b) in high glucose-induced effects in human umbilical endothelial cells at 24h. High glucose decreased cell proliferation while arresting cells in G(0)/G(1) phase of the cell cycle.

Antioxidants attenuate high glucose-induced hypertrophic growth in renal tubular epithelial cells.

Hyperglycemia-induced oxidative stress is a key mediator of renal tubular hypertrophy in diabetic nephropathy (DN). The molecular mechanisms of antioxidants responsible for inhibition of renal tubular hypertrophy in DN are incompletely characterized. We now aim at verifying the effects of N-acetylcysteine (NAC) and taurine on cellular hypertrophy in renal tubular epithelial cells under high ambient glucose.

Advanced glycation end-product-induced mitogenesis is dependent on Janus kinase 2-induced heat shock protein 70 in normal rat kidney interstitial fibroblast cells.

Kidney interstitial fibroblast proliferation is important in the pathogenesis of diabetic renal fibrosis. In this regard, advanced glycation end-product (AGE)-induced proliferation in normal rat kidney interstitial fibroblast (NRK-49F) cells is dependent on the Janus kinase 2 (JAK2) signal transducers and activators of transcription (STAT) pathway. Heat shock protein (Hsp) is a molecular target of JAK/STAT.

Role of nitric oxide in high glucose-induced mitogenic response in renal fibroblasts.

Nitric oxide (NO) has been suggested to be associated with tubulointerstitial fibrosis in diabetic nephropathy. Abnormal glucose handling in the tubulointerstitium may play an important role in the development of diabetic nephropathy. This study was designed to investigate the effect of NO generation and action in renal fibroblasts exposed to high glucose (HG).

Albumin induces cellular fibrosis by upregulating transforming growth factor-beta ligand and its receptors in renal distal tubule cells.

Albuminuria is indicative of nephropathy. However, little literature has focused on the role of albumin in renal distal tubule fibrosis. We used a well-defined distal tubule cell, Madin-Darby Canine Kidney (MDCK).

Effect of nitric oxide-cGMP-dependent protein kinase activation on advanced glycation end-product-induced proliferation in renal fibroblasts.

Renal interstitial fibrosis is believed to play a key role in the development of diabetic nephropathy (DN), and advanced glycation end-products (AGE) may contribute importantly to this. Recent reports have shown that nitric oxide (NO) is closely linked to the renal interstitial fibrosis of DN. In this study, the mechanisms by which NO and its downstream signals mediate the AGE-induced proliferative response in normal rat kidney fibroblasts (NRK-49F) are examined.

Regulation of type II transforming-growth-factor-beta receptors by protein kinase C iota.

TGF-beta (transforming growth factor-beta) is implicated in the pathogenesis of diabetic nephropathy. We previously demonstrated that up-regulation of type II TGF-beta receptor (TbetaRII) induced by high glucose might contribute to distal tubular hypertrophy [Yang, Guh, Yang, Lai, Tsai, Hung, Chang and Chuang (1998) J. Am.