Localization of SPARC in developing, mature, and chronically injured human allograft kidneys
Localization of SPARC in developing, mature, and chronically injured human allograft kidneys
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DOI：
10.1046/j.1523-1755.2002.00680.x
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发表时间：
2002-12-01
影响因子：
19.6
通讯作者：
Bassuk, JH
中科院分区：
文献类型：
--
作者：
Alpers, CE;Hudkins, KL;Bassuk, JH
背景在发育、组织重塑和修复过程中表达基质细胞蛋白-它作为细胞增殖的内源性抑制剂发挥作用，调节血管生成，调节细胞与细胞外基质的粘附，结合细胞因子如血小板衍生生长因子并刺激转化生长因子-β（TGF-β）产生。本研究描述了人肾发育过程中，在正常肾和肾移植排斥反应中的表达。共60个肾脏标本，包括肿瘤肾切除术（N = 24），胎儿肾（N = 27）和移植肾移植物（N = 9）的正常区域，被纳入本研究。使用两种不同的抗体通过免疫组织化学定位cDNA 3蛋白。在连续切片上用原位杂交法检测细胞内mRNA的表达。在正常成人肾脏中，VEGF 1蛋白表达于内脏和壁上皮细胞、集合管上皮（CD）、尿路上皮、肌性动脉平滑肌细胞和间质细胞。在肾脏发育过程中，未成熟的肾小球在其表面邻接毛细血管基底膜的内脏上皮细胞中表现出极化表达。在完全分化的肾小球中，表达模式反映了成人肾脏的表达模式。此外，输尿管芽的衍生物和动脉壁的平滑肌细胞丰富地表达了c-myc。在慢性同种异体移植排斥反应期间，在新生内膜动脉平滑肌细胞、浸润性炎性细胞以及间质纤维化区域的间质肌成纤维细胞中表达。原位杂交检测到的mRNA合成反映了这些蛋白的表达模式。这些研究共定位于先前显示为PDGF B链表达和/或活性位点的肾损伤的几个位点。我们推测，在慢性PDGF介导的硬化性间质和血管损伤中，PDGF可能作为辅助分子发挥作用。肾小球上皮细胞的定位与啮齿类动物中的类似发现相对应，并可能反映其在细胞粘附和/或细胞形状调节中的作用。
Background. The matricellular protein SPARC (secreted protein acidic and rich in cysteine) is expressed during development, tissue remodeling and repair. It functions as an endogenous inhibitor of cell proliferation, regulates angiogenesis, regulates cell adhesion to extracellular matrix, binds cytokines such as platelet derived growth factor and stimulates transforming growth factor-beta (TGF-beta) production. This study describes the expression of SPARC during human renal development, in normal kidneys and during renal allograft rejection.Methods. A total of 60 renal specimens, including normal areas from tumor nephrectomies (N = 24), fetal kidneys (N = 27) and explanted renal allografts (N = 9), were included in the study. SPARC protein was localized by immunohistochemistry using two different antibodies. On consecutive sections SPARC mRNA was detected by in situ hybridization.Results. In the normal adult kidney SPARC protein was expressed by visceral and parietal epithelial cells, collecting duct epithelium (CD), urothelium, smooth muscle cells of muscular arteries and focally in interstitial cells. During renal development immature glomeruli demonstrated a polarized SPARC expression in visceral epithelial cells at their surface abutting the capillary basement membranes. In the fully differentiated glomeruli the expression pattern mirrored that of the adult kidney. Furthermore, SPARC was abundantly expressed by derivatives of the ureteric bud, and smooth muscle cells of arterial walls. During chronic allograft rejection SPARC is expressed in neointimal arterial smooth muscle cells, infiltrating inflammatory cells as well as by interstitial myofibroblasts in areas of interstitial fibrosis. SPARC mRNA synthesis detected by in situ hybridization mirrored these protein expression patterns.Conclusion. These studies co-localize SPARC to several sites of renal injury previously shown to be sites of PDGF B-chain expression and/or activity. We speculate that SPARC could function as an accessory molecule in chronic PDGF-mediated sclerosing interstitial and vascular injury. SPARC localization to glomerular epithelial cells corresponds to similar findings in rodents, and may reflect its role in cell adhesion and /or regulation of cell shape.