Effects of diabetes and hypertension on macrophage infiltration and matrix expansion in the rat kidney

被引：37

作者：

Hartner A. ^{[1
]}

Veelken R. ^{[2
]}

Wittmann M. ^{[3
]}

Cordasic N. ^{[1
,2
]}

Hilgers K.F. ^{[2
]}

机构：

[1] Children and Youth Hospital, University of Erlangen-Nuremberg, D-91054 Erlangen

[2] Nephrology and Hypertension, University of Erlangen-Nuremberg, D-91054 Erlangen

[3] Medicine II, Augsburg City Hospital, D-86156 Augsburg

来源：

BMC Nephrology | / 6卷 / 1期

关键词：

Diabetic Nephropathy; Macrophage Infiltration; Matrix Expansion; Glomerular Tuft; Osteopontin mRNA;

D O I：

10.1186/1471-2369-6-6

中图分类号：

学科分类号：

摘要：

Background: In experimental models of diabetes mellitus, aggravation of renal injury by concomitant hypertension has been described. Inflammatory mechanisms contribute to renal damage in both diseases. We investigated whether hypertension and diabetes mellitus act synergistically to induce macrophage infiltration and matrix expansion in the kidney. Methods: Insulin-dependent diabetes mellitus was induced by streptozotocin injections to hypertensive mRen2-transgenic rats (TGR) and normotensive Sprague-Dawley control rats. Quantitative immunohistochemical examination of kidney tissue sections was used to measure macrophage infiltration and matrix expansion. The expression of MCP-1, Osteopontin, RANTES, ICAM-1 and VCAM-1 was evaluated by real-time RT-PCR. The localization of MCP-1 was studied by immunohistochemistry. Results: Macrophage infiltration was present in the kidney of normotensive diabetic rats. Hypertensive rats exhibited a more marked infiltration of macrophages, regardless of whether diabetes was present or not. Gene expression of ICAM-1, VCAM-1 and RANTES was unaltered whereas Osteopontin and MCP-1 were induced by hypertension. Immunoreactive MCP-1 was slightly increased in diabetic rat kidney podocytes, and more markedly increased in hypertensive animals. Glomerular matrix accumulation was induced by diabetes and hypertension to a similar degree, and was highest in hypertensive, diabetic animals. Conclusion: Diabetes mellitus caused a mild, and angiotensin-dependent hypertension a more marked infiltration of macrophages in the kidney. Combination of both diseases led to additive effects on matrix expansion but not on inflammation. Hypertension appears to be a much stronger stimulus for inflammation of the kidney than STZ diabetes, at least in mRen2-transgenic rats. © 2005 Hartner et al; licensee BioMed Central Ltd.

引用

共 23 条

[1]

Ritz E., Orth S.R., Nephropathy in patients with type 2 diabetes mellitus, N Engl J Med, 341, pp. 1127-1133, (1999)

[2]

Hollenberg N.K., Price D.A., Fisher N.D., Lansang M.C., Perkins B., Gordon M.S., Williams G.H., Laffel L.M., Glomerular hemodynamics and the renin-angiotensin system in patients with type 1 diabetes mellitus, Kidney Int, 63, pp. 172-178, (2003)

[3]

Hilgers K.F., Hartner A., Porst M., Mai M., Wittmann M., Hugo C., Ganten D., Geiger H., Veelken R., Mann J.F., Monocyte chemoattractant protein-1 and macrophage infiltration in hypertensive kidney injury, Kidney Int, 58, pp. 2408-2419, (2000)

[4]

Wolf G., Ziyadeh F.N., Thaiss F., Tomaszewski J., Caron R.J., Wenzel U., Zahner G., Helmchen U., Stahl R.A., Angiotensin II stimulates expression of the chemokine RANTES in rat glomerular endothelial cells. Role of the angiotensin type 2 receptor, J Clin Invest, 100, pp. 1047-1058, (1997)

[5]

Capers Q., Alexander R.W., Lou P., De Leon H., Wilcox J.N., Ishizaka N., Howard A.B., Taylor W.R., Monocyte chemoattractant protein-1 expression in aortic tissues of hypertensive rats, Hypertension, 30, pp. 1397-1402, (1997)

[6]

Ihm C.G., Park J.K., Hong S.P., Lee T.W., Cho B.S., Kim M.J., Cha D.R., Ha H., A high glucose concentration stimulates the expression of monocyte chemotactic peptide 1 in human mesangial cells, Nephron, 79, pp. 33-37, (1998)

[7]

Young B.A., Johnson R.J., Alpers C.E., Eng E., Gordon K., Floege J., Couser W.G., Seidel K., Cellular events in the evolution of experimental diabetic nephropathy, Kidney Int, 47, pp. 935-944, (1995)

[8]

Wada T., Furuichi K., Sakai N., Iwata Y., Yoshimoto K., Shimizu M., Takeda S.I., Takasawa K., Yoshimura M., Kida H., Kobayashi K.I., Mukaida N., Naito T., Matsushima K., Yokoyama H., Up-regulation of monocyte chemoattractant protein-1 in tubulointerstitial lesions of human diabetic nephropathy, Kidney Int, 58, pp. 1492-1499, (2000)

[9]

Kato S., Luyckx V.A., Ots M., Lee K.W., Ziai F., Troy J.L., Brenner B.M., MacKenzie H.S., Renin-angiotensin blockade lowers MCP-1 expression in diabetic rats, Kidney Int, 56, pp. 1037-1048, (1999)

[10]

Banba N., Nakamura T., Matsumura M., Kuroda H., Hattori Y., Kasai K., Possible relationship of monocyte chemoattractant protein-1 with diabetic nephropathy, Kidney Int, 58, pp. 684-690, (2000)

← 1 2 3 →