Increased vascular permeability and severe renal tubular damage after ischemia-reperfusion injury in mice lacking adiponectin or T-cadherin
Adiponectin (APN) is a circulating protein specifically produced by adipocytes. Native APN specifically binds to T-cadherin, a glycosylphosphatidylinositol-anchored protein, mediating the exosome-stimulating effects of APN in endothelial, muscle, and mesenchymal stem cells. It was previously reported that APN has beneficial effects on kidney diseases, but the role of T-cadherin has not been clarified yet. Here, our immunofluorescence study indicated the existence of both T-cadherin and APN protein in pericytes, subsets of tissue-resident mesenchymal stem/progenitor cells positive for PDGFRβ, surrounding peritubular capillaries. In an acute renal ischemia-reperfusion (I/R) model, T-cadherin-KO mice, similar to APN-KO mice, exhibited the more progressive phenotype of renal tubular damage and increased vascular permeability than wild-type mice. In addition, in response to I/R injury, the renal PDGFRβ-positive cell area increased in wild-type mice, but opposingly decreased both in Tcad-KO and APN-KO mice, suggesting severe pericyte loss. Mouse primary pericytes also expressed T-cadherin. APN promoted exosome secretion in a T-cadherin-dependent manner. Such exosome production from pericytes may play an important role in maintaining the capillary network and APN-mediated inhibition of renal tubular injury. In summary, our study suggested that APN protected the kidney in an acute renal injury model by binding to T-cadherin.