Periostin induces proliferation of human autosomal dominant polycystic kidney cells through αV-integrin receptor
Periostin induces proliferation of human autosomal dominant polycystic kidney cells through αV-integrin receptor
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DOI：
10.1152/ajprenal.90266.2008
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发表时间：
2008-11-01
影响因子：
4.2
通讯作者：
Yamaguchi, Tamio
中科院分区：
文献类型：
--
作者：
Wallace, Darren P.;Quante, Megan T.;Yamaguchi, Tamio
Wallace DP、Quante MT、Reif GA、Nivens E、Ahmed F、Hempson SJ、Blanco G、Yamaguchi T.Periostin通过α(V)-整合素受体诱导常染色体显性多囊肾细胞增殖。AM J Physiol Renal Physiol 295：F1463-F1471,2008。2008年8月27日首次出版；doi：10.1152/ajprenal.90266.2008。常染色体显性遗传性多囊肾病(ADPKD)的主要病理生理特征是由于大量充满液体的囊肿所导致的进行性肾脏增大。这些上皮性肿瘤扩张缓慢，损害非囊性实质的机制尚未明确。在培养的人ADPKD囊上皮细胞的微阵列分析中，Periostin mRNA的过度表达是正常人类肾脏(NHK)细胞的15倍。Periostin最初在成骨细胞中发现，在正常成人肾脏中不表达，但在肾脏发育过程中短暂表达。我们发现Periostin存在于囊壁细胞、邻近囊壁的细胞外基质和囊液中。ADPKD细胞通过管腔和基底侧质膜分泌Periostin。Periostin可使囊性上皮细胞增殖增加27.9%/-3.1%(P<；0.001)，并促进体外囊性生长，但不影响正常肾细胞的增殖。在ADPKD细胞中，Periostin受体α(V)-整合素的表达是NHK细胞的9倍，并且阻断α(V)-整合素的抗体抑制了Periostin诱导的细胞增殖。我们的结论是，Periostin是一种由壁上皮细胞分泌的新的自分泌有丝分裂原，具有加速ADPKD囊性生长和促进间质重塑的潜力。
Wallace DP, Quante MT, Reif GA, Nivens E, Ahmed F, Hempson SJ, Blanco G, Yamaguchi T. Periostin induces proliferation of human autosomal dominant polycystic kidney cells through alpha(V)-integrin receptor. Am J Physiol Renal Physiol 295: F1463-F1471, 2008. First published August 27, 2008; doi:10.1152/ajprenal.90266.2008. Progressive renal enlargement due to the growth of innumerable fluid-filled cysts is a central pathophysiological feature of autosomal dominant polycystic kidney disease (ADPKD). These epithelial neoplasms enlarge slowly and damage noncystic parenchyma by mechanisms that have not been clearly defined. In a microarray analysis of cultured human ADPKD cyst epithelial cells, periostin mRNA was overexpressed 15-fold compared with normal human kidney (NHK) cells. Periostin, initially identified in osteoblasts, is not expressed in normal adult kidneys but is expressed transiently during renal development. We found periostin in cyst-lining cells in situ in the extracellular matrix adjacent to the cysts and within cyst fluid. ADPKD cells secreted periostin across luminal and basolateral plasma membranes. Periostin increased proliferation of cyst epithelial cells 27.9 +/- 3.1% (P < 0.001) above baseline and augmented in vitro cyst growth but did not affect proliferation of normal renal cells. Expression of alpha(V)-integrin, a periostin receptor, was ninefold higher in ADPKD cells compared with NHK cells, and antibodies that block alpha(V)-integrin inhibited periostin-induced cell proliferation. We conclude that periostin is a novel autocrine mitogen secreted by mural epithelial cells with the potential to accelerate cyst growth and promote interstitial remodeling in ADPKD.