Ghrelin Attenuates Renal Fibrosis and Inflammation of Obstructive Nephropathy

Abstract

Ghrelin is a gastric peptide that modulates multiple biological functions, of which the stimulation of food intake is the most well-known function. Ghrelin also exerts potential anti-inflammatory and antifibrotic properties in different organs but to our knowledge whether ghrelin inhibits the progression of renal fibrosis is unknown. Thus, we investigated the effect and underlying mechanisms of ghrelin in a rat model of renal fibrosis. Male Sprague Dawley® rats were divided into 4 groups, including vehicle or ghrelin treated sham operated groups and vehicle or ghrelin treated unilateral ureteral obstruction groups. Kidneys harvested on postoperative day 7 or 14 were evaluated for renal inflammation, fibrosis and apoptosis, and the expression of profibrotic and proinflammatory factors. Ghrelin inhibited renal fibrosis by attenuating collagen production, extracellular matrix deposition, and α-smooth muscle actin and fibronectin expression. Ghrelin administration decreased macrophage infiltration and several proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1β and monocyte chemotactic protein-1, as well as phosphorylated nuclear factor-κB p65. Ghrelin also inhibited myofibroblast accumulation by blocking the transforming growth factor-β1/Smad3 signaling pathway. Furthermore, ghrelin attenuated renal tubular cell apoptosis and epithelial-mesenchymal transition processes induced by unilateral ureteral obstruction injury. These findings indicate that ghrelin is a potent antifibrotic agent that may have therapeutic potential in patients with obstructive nephropathy.