Early Differential Expression of Oncostatin M in Obstructive Nephropathy
Early Differential Expression of Oncostatin M in Obstructive Nephropathy
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DOI：
10.1089/jir.2009.0105
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发表时间：
2010-07-01
影响因子：
2.3
通讯作者：
Smith, C. Wayne
中科院分区：
文献类型：
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作者：
Elbjeirami, Wafa M.;Truong, Luan D.;Smith, C. Wayne
间质纤维化在肾脏疾病的进展中起主要作用。抑瘤素M（OSM）是一种调节细胞存活、分化和增殖的细胞因子。检测慢性阻塞性肾病患者肾组织中OSM的表达。在患病的人肾脏中升高的水平表明OSM水平与肾组织纤维化之间可能存在相关性。事实上，单侧输尿管梗阻（UUO），一种肾纤维化模型，在UUO后数小时内以时间依赖性方式增加OSM和OSM受体（OSM-R）表达。在体外，OSM在肾小管上皮细胞（TECs）的过度表达导致上皮-肌成纤维细胞转分化。cDNA微阵列技术鉴定了与假手术肾相比，阻塞肾中免疫调节剂的表达上调。在体外，OSM处理上调肾成纤维细胞中CC趋化因子配体CCL 7和CXC趋化因子配体（CXCL）-14 mRNA。在体内，用中和性抗OSM抗体治疗UUO小鼠降低肾趋化因子表达。总之，OSM在尿路梗阻后早期肾组织中上调。因此，OSM可能通过诱导TECs的肌成纤维细胞转分化以及白细胞浸润在肾纤维化的发生中起重要作用。这一过程反过来可能部分促进梗阻性肾病的进展，并使OSM成为肾纤维化的一个有前途的治疗靶点。
Interstitial fibrosis plays a major role in progression of renal diseases. Oncostatin M (OSM) is a cytokine that regulates cell survival, differentiation, and proliferation. Renal tissue from patients with chronic obstructive nephropathy was examined for OSM expression. The elevated levels in diseased human kidneys suggested possible correlation between OSM level and kidney tissue fibrosis. Indeed, unilateral ureteral obstruction (UUO), a model of renal fibrosis, increased OSM and OSM receptor (OSM-R) expression in a time-dependent manner within hours following UUO. In vitro, OSM overexpression in tubular epithelial cells (TECs) resulted in epithelial-myofibroblast transdifferentiation. cDNA microarray technology identified up-regulated expression of immune modulators in obstructed compared with sham-operated kidneys. In vitro, OSM treatment up-regulated CC chemokine ligand CCL7, and CXC chemokine ligand (CXCL)-14 mRNA in kidney fibroblasts. In vivo, treatment of UUO mice with neutralizing anti-OSM antibody decreased renal chemokines expression. In conclusion, OSM is up-regulated in kidney tissue early after urinary obstruction. Therefore, OSM might play an important role in initiation of renal fibrogenesis, possibly by inducing myofibroblast transdifferentiation of TECs as well as leukocyte infiltration. This process may, in turn, contribute in part to progression of obstructive nephropathy and makes OSM a promising therapeutic target in renal fibrosis.