Overexpression of histamine H4 receptors in the kidney of diabetic rat

Objective and design: The renal expression of H1 and H2 receptors was previously demonstrated, while that of the H4 receptor has been poorly investigated, thus the aim of this research was to investigate the expression of the H4 receptor in the kidney of diabetic rats. Material or subjects: 24 8-week-old male Wistar rats Treatment: Diabetes was induced in 12 rats by a single i.v. injection of streptozotocin, and animals were sacrificed 6 weeks later. Methods: Kidneys were collected and processed for quantitative PCR or immunohistochemical analyses. To ascertain the renal topology of the H4 receptor, colocalization experiments were performed with a series of markers. Results: H4 receptor is expressed in healthy rats, although at a very low level, and is profoundly upregulated in diabetic animals. Immunohistochemical analysis revealed the highest immune-positivity in the medulla. Colocalization experiments revealed a close overlap in expression topology of the H4 receptor and both Tamm-Horsfall glycoprotein and aquaporin 1 was observed. Conclusions: The results demonstrate, for the first time, that the H4 receptor is expressed in the kidney mainly by resident renal cells of the loop of Henlé and that this receptor is significantly overexpressed in diabetic animals, thus suggesting a possible role in the pathogenesis of diabetes-associated renal disease.