Significance of Osteopontin Expression in the Progression of Human Focal Segmental Glomerulosclerosis
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Background : Osteopontin (OPN) is a cytokine related to cell-matrix adhesion and cell survival and is expressed in the distal convoluted tubules in normal adult kidneys. Only one in vitro study has investigated the role of OPN in mechanically stretched podocytes and their actin cytoskeleton rearrangement. Methods : Glomerular OPN expression was investigated in biopsies from patients with human idiopathic focal segmental glomerulosclerosis (FSGS) (n = 25) and in normal renal biopsies (n = 16) by immunohistochemistry. Results : OPN was expressed in the podocytes from patients with FSGS. OPN expression increased in podocytes from both non-sclerotic hypertrophic and sclerotic glomerular tufts in patients with FSGS compared to the podocytes in normal controls. Conclusions : The results suggest that OPN plays a role in the early adaptive response of podocytes to the increased mechanical load caused by glomerular hypertrophy preceding FSGS. OPN was involved in cell-matrix adhesion and influenced the detachment delay of podocytes from the glomerular basement membrane and apoptosis.
Abstract
Background : Osteopontin (OPN) is a cytokine related to cell-matrix adhesion and cell survival and is expressed in the distal convoluted tubules in normal adult kidneys. Only one in vitro study has investigated the role of OPN in mechanically stretched podocytes and their actin cytoskeleton rearrangement. Methods : Glomerular OPN expression was investigated in biopsies from patients with human idiopathic focal segmental glomerulosclerosis (FSGS) (n = 25) and in normal renal biopsies (n = 16) by immunohistochemistry. Results : OPN was expressed in the podocytes from patients with FSGS. OPN expression increased in podocytes from both non-sclerotic hypertrophic and sclerotic glomerular tufts in patients with FSGS compared to the podocytes in normal controls. Conclusions : The results suggest that OPN plays a role in the early adaptive response of podocytes to the increased mechanical load caused by glomerular hypertrophy preceding FSGS. OPN was involved in cell-matrix adhesion and influenced the detachment delay of podocytes from the glomerular basement membrane and apoptosis.
참고문헌 (30)
- Denhardt DT, "Osteopontin-induced modifications of cellular functions", Ann N Y Acad Sci, 760, pp.127~142 (1995)
- Hampel DJ, "Osteopontin traffic in hypoxic renal epithelial cells", Nephron Exp Nephrol, 94, pp.e66~e76 (2003)
- Endlich N, "Analysis of differential gene expression in stretched podocytes:osteopontin enhances adaptation of podocytes to mechanical stress", FASEB J, 16, pp.1850~1852 (2002)
- Faul C, "Actin up:regulation of podocyte structure and function by components of the actin cytoskeleton", Trends Cell Biol, 17, pp.428~437 (2007)
- Ijpelaar DH, "Glomerular hypertrophy precedes albuminuria and segmental loss of podoplanin in podocytes in Munich-Wistar-Frömter rats", Am J Physiol Renal Physiol, 294, pp.F758~F767 (2008)
- Hartner A, "Glomerular osteopontin expression and macrophage infiltration in glomerulosclerosis of DOCA-salt rats", Am J Kidney Dis, 38, pp.153~164 (2001)
- Xie Y, "Expression,roles,receptors,and regulation of osteopontin in the kidney", Kidney Int, 60, pp.1645~1657 (2001)
- Lane PH, "Estimation of glomerular volume:a comparison of four methods", Kidney Int, 41, pp.1085~1089 (1992)
- D’Agati VD, "The spectrum of focal segmental glomerulosclerosis:new insights", Curr Opin Nephrol Hypertens, 17, pp.271~281 (2008)
- Lee HS, "The significance of glomerular hypertrophy in focal segmental glomerulosclerosis", Clin Nephrol, 44, pp.349~355 (1995)
- Kriz W, "The pathogenesis of ‘classic’ focal segmental glomerulosclerosis- lessons from rat models", Nephrol Dial Transplant, 18(Suppl 6), pp.vi39~449 (2003)
- Wiggins RC, "The spectrum of podocytopathies:a unifying view of glomerular diseases", Kidney Int, 71, pp.1205~1214 (2007)
- Bennett MR, "Laser capture microdissection-microarray analysis of focal segmental glomerulosclerosis glomeruli", Nephron Exp Nephrol, 107, pp.e30~e40 (2007)
- Endlich N, "Podocytes respond to mechanical stress in vitro", J Am Soc Nephrol, 12, pp.413~422 (2001)
- Weber GF, "Receptor-ligand interaction between CD44 and osteopontin(Eta-1)", Science, 271, pp.509~512 (1996)
- Denhardt DT, "Osteopontin as a means to cope with environmental insults:regulation of inflammation,tissue remodeling,and cell survival", J Clin Invest, 107, pp.1055~1061 (2001)
- Unger GM, "Quantitative assessment of leading edge adhesion:reattachment kinetics modulated by injury-derived intracellular calcium predict wound closure rates in endothelial monolayers", J Cell Physiol, 174, pp.217~231 (1998)
- Kawasaki J, "Regulation of Ca2+-dependent K+ current by alphavbeta3 integrin engagement in vascular endothelium", J Biol Chem, 279, pp.12959~12966 (2004)
- Morton MJ, "Human podocytes possess a stretch-sensitive,Ca2+-activated K+ channel:potential implications for the control of glomerular filtration", J Am Soc Nephrol, 15, pp.2981~2987 (2004)
- 윤길숙, "신세포암종에서 이형 CD44 단백 발현의 의의", The Korean Journal of Pathology, 39(4), pp.251~257 (2005), 대한병리학회
- Nakamura H, "Roles of and correlation between alpha-smooth muscle actin,CD44,hyaluronic acid and osteopontin in crescent formation in human glomerulonephritis", Clin Nephrol, 64, pp.401~411 (2005)
- Lan HY, "De novo glomerular osteopontin expression in rat crescentic glomerulonephritis", Kidney Int, 53, pp.136~145 (1998)
- Teramoto H, "Autocrine activation of an osteopontin-CD44-Rac pathway enhances invasion and transformation by H-RasV12", Oncogene, 24, pp.489~501 (2005)
- Shui HA, "Osteopontin as an injury marker expressing in epithelial hyperplasia lesions helpful in prognosis of focal segmental glomerulosclerosis", Transl Res, 150, pp.216~222 (2007)
- Smeets B, "Renal progenitor cells contribute to hyperplastic lesions of podocytopathies and crescentic glomerulonephritis", J Am Soc Nephrol, 20, pp.2593~2603 (2009)
- Lopez CA, "Heterogeneity of osteopontin expression among nephrons in mouse kidneys and enhanced expression in sclerotic glomeruli", Lab Invest, 69, pp.355~363 (1993)
- Hudkins KL, "Osteopontin expression in human cyclosporine toxicity", Kidney Int, 60, pp.635~640 (2001)
- Faul C, "The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A", Nat Med, 14, pp.931~938 (2008)
- Thomas SE, "Tubulointerstitial disease in aging:evidence for underlying peritubular capillary damage,a potential role for renal ischemia", J Am Soc Nephrol, 9, pp.231~242 (1998)
- 홍희연, "신세포암종에서 Osteopontin 발현의 예후 인자로서 의의", The Korean Journal of Pathology, 40(3), pp.225~230 (2006), 대한병리학회