Succinate, an intermediate metabolite of the Krebs cycle, can alter metabolomics response to certain drugs and controls array molecular responses in urothelium through activation its receptor, G-protein coupled receptor 91 (GPR91). Mirabegron, a β3-adrenergic (β3-AR) agonist used treat overactive bladder syndrome (OAB), increases intracellular cAMP detrusor smooth muscle cells (SM...

Micro-vascular complications such as diabetic nephropathy (DN) develop in patients with uncontrolled T1DM. Low density lipoprotein receptor-related protein 5 (LRP5) is the co-receptor ligand of Wnt signaling pathway. Many single nucleotide variants have been identified human LRP5 gene and were reported to be associated metabolic disorders. The Wnt/β-catenin pathway has proposed play an importan...

BACKGROUND Phosphorylation of G protein coupled receptors (GPCRs) by G protein coupled receptor kinases (GRKs) and the subsequent recruitment of β-arrestins are important for their desensitization. Using shRNA-mediated gene silencing strategy, we have recently shown that GRK2, GRK3 and β-arrestin-2 promote C3a receptor (C3aR) desensitization in human mast cells. We also demonstrated that β-arre...

The lymphotoxin signaling pathway plays an important role in the homeostasis and function of peripheral and mucosal dendritic cells, and dendritic cell-intrinsic lymphotoxin β receptor expression is required for optimal responses to opportunistic intestinal bacteria. However, it is unknown whether dendritic cell-intrinsic lymphotoxin β receptor signaling is required for responses to intestinal ...

β-Adrenergic receptor blockers (β-blockers) are commonly used to treat heart failure, but the biologic mechanisms governing their efficacy are still poorly understood. The complexity of β-adrenergic signaling coupled with the influence of receptor polymorphisms makes it difficult to intuit the effect of β-blockers on cardiac physiology. While some studies indicate that β-blockers are efficaciou...

INTRODUCTION Systemic sclerosis (SSc) is a complex and not fully understood autoimmune disease associated with fibrosis of multiple organs. The main effector cells, the myofibroblasts, are collagen-producing cells derived from the activation of resting fibroblasts. This process is regulated by a complex repertoire of profibrotic cytokines, and among them transforming growth factor beta (TGF-β) ...

β-glucans exert receptor-mediated immunomodulating activities, including oxidative burst activity and cytokine secretion. The role of the β-glucan receptors dectin-1 and complement receptor 3 (CR3) in the response of immune cells towards β-glucans is still unresolved. Dectin-1 is considered as the main β-glucan receptor in mice, while recent studies in man show that CR3 is more important in β-g...

Re-epithelialization begins early during skin wound healing and is regulated by various growth factors and cytokines. Angiotensin II promotes the migration of keratinocytes and thereby contributes to wound healing. We investigated the mechanism by which angiotensin II stimulates human keratinocyte migration. Angiotensin II-induced keratinocyte migration was inhibited by an angiotensin II type 1...

Arteriolar hyalinosis is a common histological finding in renal transplant recipients treated with the calcineurin inhibitor tacrolimus; however, the pathophysiologic mechanisms remain unknown. In addition to increasing transforming growth factor (TGF)-β levels, tacrolimus inhibits calcineurin by binding to FK506-binding protein 12 (FKBP12). FKBP12 alone also inhibits TGF-β receptor activation....