Expression and role of adiponectin receptor 1 in lipopolysaccharide-induced proliferation of cultured rat adventitial fibroblasts

Abstract

Adiponectin is an adipose-derived hormone that has anti-diabetic and anti-atherogenic effects through interaction with AdipoR1 and AdipoR2 (adiponectin receptors 1 and 2), but little is known about the expression and function of adiponectin and its receptors in adventitia and adventitial fibroblasts. In the present study, we have demonstrated that AdipoR1 is highly expressed in rat adventitia and cultured adventitial fibroblasts by quantitative real-time PCR, Western blotting and immunofluorescent staining, whereas Adipo2 is low-expressed. The expression of AdipoR1 have been observed to decrease gradually in adventitial fibroblasts in response to LPS (lipopolysaccharide) treatment. No local expression of adiponectin has been detected in adventitial tissues, indicating that serum adiponectin is the ligand for AdipoR1 in adventitial fibroblasts. In addition, treatment of recombinant adiponectin inhibited LPS-induced proliferation of adventitial fibroblasts via activation of the AMPK (adenosine monophosphate-activated protein kinase). AdipoR1 siRNA (small interfering RNA) transfection potently knocked down the receptor protein. The siRNA-AdipoR1 transfected cells and AMPK inhibitor compound C treated cells showed decreased phosphorylated level of AMPK as determined by Western blot analysis, and increased the proliferation of adventitial fibroblasts as determined by BrdU (5-bromo-29-deoxyuridine) staining. These results demonstrated that adiponectin stimulates the proliferation of adventitial fibroblasts via the AdipoR1 and AMPK signalling pathways.