OBJECTIVE The transcription factor peroxisome proliferator-activated receptor (PPAR)-gamma plays an important role in controlling cell differentiation. The aim of the present study was to examine whether PPAR-gamma expression was reduced in skin scleroderma fibroblasts and whether PPAR-gamma agonists could suppress the persistent fibrotic phenotype of skin scleroderma fibroblasts. METHODS Der...

Thiazolidinediones (TZDs), synthetic ligands of peroxisome proliferator-activated receptor (PPAR)-gamma, are known to decrease hepatic glucose production and increase glycogen synthesis in diabetic animals. Recently it was reported that glucokinase (GK) expression was increased by TZDs in the liver of diabetic ZDF rats. However, the mechanism whereby TZDs increase GK expression is not yet studi...

Diabetes is associated with increased formation of advanced glycation end products (AGEs), which have been implicated in micro and macrovascular complications of diabetes. Our earlier reports showed proangiogenic effect of AGE-bovine serum albumin (BSA). In order to understand the mechanism of AGE-mediated angiogenesis, the possibility of involvement of peroxisome prolifeator activated receptor...

Bone loss with aging results from attenuated and unbalanced bone turnover that has been associated with a decreased number of bone forming osteoblasts, an increased number of bone resorbing osteoclasts, and an increased number of adipocytes (fat cells) in the bone marrow. Osteoblasts and adipocytes are derived from marrow mesenchymal stroma/stem cells (MSC). The milieu of intracellular and extr...

Peroxisome proliferator-activated receptors (PPAR) are nuclear receptors acting as transcription factors on numerous target genes after heterodimerization with the retinoid X receptor. PPAR-alpha and PPAR-gamma may be activated by different agonists, although the endogenous ligands are unknown. Although PPAR-alpha is mainly involved in fatty acid oxidation and expressed in liver, kidney, and sk...

The synthesis and structure-activity relationships of a novel series of N-sulfonyl-2-indole carboxamides that bind to peroxisome proliferator-activated receptor gamma (PPAR-gamma) are reported. Chemical optimization of the series led to the identification of 4q (IC(50)=50 nM) as a potent binding agent of PPAR-gamma. Also reported is preliminary cell based data suggesting the use of these compou...

Peroxisomal proliferator-activated receptors (PPARs) belong to a nuclear receptor superfamily of ligand-activated transcription factors. The PPAR-gamma isoform is expressed in human T lymphocytes, and oral administration of PPAR-gamma agonists ameliorates the clinical course and histopathological features in experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis, sugg...

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone-receptor superfamily. Originally cloned in 1990, PPARs were found to be mediators of pharmacologic agents that induce hepatocyte peroxisome proliferation. PPARs also are expressed in cells of the cardiovascular system. PPAR gamma appears to be highly expressed during atherosclerotic lesion formation, suggesting th...

Peroxisome proliferator-activated receptor (PPAR)-gamma plays an important role in adipogenesis. However, the functions of PPAR-gamma in differentiated adipocytes have remained unclear. The role of PPAR-gamma in mature 3T3-L1 adipocytes was therefore investigated by overexpression of a dominant negative mutant of this protein (PPAR-gamma-DeltaC) that lacks the 16 COOH-terminal amino acids and t...