Pathogenic role of mast cells in the development of diabetic nephropathy: a study of patients at different stages of the disease

Abstract

Aims/hypothesis Increased renal mast cells have been detected in diabetic nephropathy. However, only a few patients have been examined. Evidence of the involvement of mast cells in diabetic nephropathy is still scarce, and no observation of mast cells during the development of diabetic nephropathy has yet been reported in humans. Here, we examined changes in renal mast cells in patients at different stages of diabetic nephropathy and related these to the development of the disease. Methods Eighty patients at different clinical stages of diabetic nephropathy and 16 normal kidney donors were recruited. Immunohistochemical staining for tryptase, chymase, TGF-β1, renin and TNF-α was done on renal sections from patients and control participants. Changes in mast cell number, degranulation, subtype and phenotype were examined. Correlation between mast cells and patients' clinical and pathological indices was analysed. Results With progression of diabetic nephropathy, the number and degranulation level of mast cells increased. Increase in mast cell number and degranulation level correlated significantly with tubular interstitial injury. Almost all renal mast cells in patients with diabetic nephropathy were found to produce chymase, renin, TGF-β1 and TNF-α. The level of TNF-α in mast cells increased with progression of diabetic nephropathy. Conclusions/interpretation This study suggests that mast cells are involved in development of diabetic nephropathy. Through release of bioactive substances, such as tryptase, chymase, TGF-β1, renin and TNF-α, into the tubular interstitium by degranulation, mast cells could promote renal inflammation and fibrosis, and thus contribute to diabetic nephropathy.

Overexpression of histamine H4 receptors in the kidney of diabetic rat

“…This idea is in keeping with the presence of mast cells, not only in the periglomerular and perivascular area, but also in the tubulointerstitium and, occasionally, in the wall of atrophied tubules [12]. Thus, a possible role of histamine released by mast cells and of the H 4 receptor in the tubular interstitium in promoting renal inflammation and fibrosis [11,12] would be an intriguing hypothesis.…”

“…Moreover, parallel to the enhanced HDC enzyme activity [8], an increase in number and degranulation of mast cells was also demonstrated in the diabetic kidney [10][11][12]. The resulting higher histamine renal content was previously linked to the microvascular diabetes-associated changes in the glomerulus, where the expression of only H 1 and H 2 receptors was demonstrated [3,13,40].…”

“…Thus, a possible role of histamine released by mast cells and of the H 4 receptor in the tubular interstitium in promoting renal inflammation and fibrosis [11,12] would be an intriguing hypothesis. Notably, the H 4 receptor is exquisitely sensitive to local histamine levels [42].…”

“…It is well recognized that in the normal kidney, mast cells are constitutively present at low numbers. However, their density and activation increase in the renal cortical tubulointerstitium and in the periglomerular and perivascular area, but not in glomeruli, in a variety of human renal diseases, including diabetic nephropathy [10][11][12].…”

Thyroid Status and Its Correlation With the Functional Activity of Immunocytes

“…Очаговая мастоцитарная инфильтрация стромы ЩЖ и окружающей жировой клетчатки с при-знаками парциальной дегрануляции МС может свидетельствовать об активизации и важной роли МС в иммунопатогенезе АИЗЩЖ. Роль МС в развитии воспаления в органах-мишенях при аутоиммунных эндокринопатиях подтверждена в недавних исследованиях у пациентов с диабети-ческой нефропатией [23]. Однако до настоящего времени точно неизвестен механизм активации МС и их роль при АИЗЩЖ [11,16].…”