Overexpression of histamine H4 receptors in the kidney of diabetic rat

Abstract

Objective and design: The renal expression of H 1 and H 2 receptors was previously demonstrated, while that of the H 4 receptor has been poorly investigated, thus the aim of this research was to investigate the expression of the H 4 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 H 4 receptor, colocalization experiments were performed with a series of markers.Results: H 4 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 H 4 receptor and both Tamm-Horsfall glycoprotein and aquaporin 1 was observed.Conclusions: The results demonstrate, for the first time, that the H 4 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.

Histamine receptor expression in human renal tubules: a comparative pharmacological evaluation

“…These data extend the previous findings on the localization of H 1 R and H 2 R in mammalian glomeruli [2,13,36] to other nephron components, such as tubular epithelial cells. Moreover, we extended our recent observation on H 4 R expression in the kidney of rats [14], now demonstrating its expression on human proximal tubular cells. Although we previously reported that in the kidney of rats the H 4 R is expressed by resident renal cells of the loop of Henlé, and not by proximal tubular cells as observed in humans, these two apparently contrasting observations are in keeping with the intra-species differences of H 4 R expression already widely reported [16].…”

“…Conventional immunohistochemical procedures were employed as described previously [14,29,30]. Briefly, immunoperoxidase staining for H 1 R, H 2 R, H 3 R and H 4 R was performed on 5 µm sections for formalin-fixed tissue from 12 patients who underwent elective nephrectomy as first line therapy for renal carcinoma at the Urology Surgery of the A.O.U.…”

“…Recently, a possible role for H 4 R has been suggested by our research group [14]. While a very low mRNA level of the latest discovered histamine receptor has been reported in the kidney of dog, monkey, rat, mouse, guinea pig and pig [15][16][17][18][19][20], in 2013 we demonstrated the presence of H 4 R in resident renal cells of the loop of Henlé!and its profound upregulation in the kidney of diabetic rats [14]. Notably, these data provide the first basis to hypothesize a possible involvement of H 4 R in the onset/progression of diabetes-associated renal disease.…”

H3 receptor renal expression in normal and diabetic rats

“…Recently, our group demonstrated the presence of the histamine H 4 receptor (H 4 R) in resident renal cells of the loop of Henlé and its profound upregulation in the kidney of diabetic rats [1]. This observation adds to independent evidence of a role for histamine in renal (patho)physiology.…”

“…Animals, protocols, diabetes induction, biochemical and histological parameters have been previously reported [1].…”