Relaxin Family Member Insulin-Like Peptide 6 Ameliorates Cardiac Fibrosis and Prevents Cardiac Remodeling in Murine Heart Failure Models.

Background: The insulin/insulin-like growth factor/relaxin family represents a group of structurally related but functionally diverse proteins. The family member relaxin-2 has been evaluated in clinical trials for its efficacy in the treatment of acute heart failure. In this study, we assessed the role of insulin-like peptide 6 (INSL6), another member of this protein family, in murine heart failure models using genetic loss-of-function and protein delivery methods.

Genetic deficiency of Wnt5a diminishes disease severity in a murine model of rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic inflammation of the joints, leading to bone erosion and joint dysfunction. Despite the recent successes of disease-modifying anti-rheumatic drugs (DMARDs), there is still clinical need for understanding the development and molecular etiology of RA. Wnts are developmental morphogens whose roles in adult pathology are poorly characterized.

The injury-induced myokine insulin-like 6 is protective in experimental autoimmune myositis.

Background: The idiopathic inflammatory myopathies represent a group of autoimmune diseases that are characterized by lymphocyte infiltration of muscle and muscle weakness. Insulin-like 6 (Insl6) is a poorly characterized member of the insulin-like/relaxin family of secreted proteins, whose expression is upregulated upon acute muscle injury.

Methods: In this study, we employed Insl6 gain or loss of function mice to investigate the role of Insl6 in a T cell-mediated model of experimental autoimmune myositis (EAM).

Divergent roles for adiponectin receptor 1 (AdipoR1) and AdipoR2 in mediating revascularization and metabolic dysfunction in vivo.

Adiponectin is a well described anti-inflammatory adipokine that is highly abundant in serum. Previous reports have found that adiponectin deficiency promotes cardiovascular and metabolic dysfunction in murine models, whereas its overexpression is protective. Two candidate adiponectin receptors, AdipoR1 and AdipoR2, are uncharacterized with regard to cardiovascular tissue homeostasis, and their in vivo metabolic functions remain controversial.

Cardiometabolic effects of adiponectin.

Over the past two decades, adiponectin has been studied in more than eleven thousand publications. A classical adipokine, adiponectin was among the first factors secreted from adipose tissue that were found to promote metabolic function. Circulating levels of adiponectin consistently decline with increasing body mass index.

T-cadherin is essential for adiponectin-mediated revascularization.

Adipose tissue secretes protein factors that have systemic actions on cardiovascular tissues. Previous studies have shown that ablation of the adipocyte-secreted protein adiponectin leads to endothelial dysfunction, whereas its overexpression promotes wound healing. However, the receptor(s) mediating the protective effects of adiponectin on the vasculature is not known.