Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
PLoS One. 2012;7(10):e48164. doi: 10.1371/journal.pone.0048164. Epub 2012 Oct 24.
Reduced turnover of extracellular matrix has a role in renal fibrosis. Matrix metalloproteinases (MMPs) is associated with many glomerular diseases, but the histological association of MMPs and human renal fibrosis is unclear.
This is a retrospective study. Institutional Review Board approval was obtained for the review of patients' medical records, data analysis and pathological specimens staining with waiver of informed consents. Specimens of forty-six patients were examined by immunohistochemical stain of MMP-9 in nephrectomized kidneys, and the association of renal expression of MMP-9 and renal fibrosis was determined. MMP-9 expression in individual renal components and fibrosis was graded as high or low based on MMP-9 staining and fibrotic scores.
Patients with high interstitial fibrosis scores (IFS) and glomerular fibrosis scores (GFS) had significantly higher serum creatinine, lower estimated glomerular filtration rate (eGFR), and were more likely to have chronic kidney disease (CKD) and urothelial cell carcinoma. Univariate analysis showed that IFS and GFS were negatively associated with normal and atrophic tubular cytoplasmic MMP-9 expression and IFS was positively correlated with atrophic tubular nuclear MMP-9 expression. Multivariate stepwise regression indicated that MMP-9 expression in atrophic tubular nuclei (r = 0.4, p = 0.002) was an independent predictor of IFS, and that MMP-9 expression in normal tubular cytoplasm (r = -0.465, p<0.001) was an independent predictor of GFS.
Interstitial fibrosis correlated with MMP-9 expression in the atrophic tubular nuclei. Our results indicate that renal fibrosis is associated with a decline of MMP-9 expression in the cytoplasm of normal tubular cells and increased expression of MMP-9 in the nuclei of tubular atrophic renal tubules.
细胞外基质周转率降低与肾纤维化有关。基质金属蛋白酶（MMPs）与许多肾小球疾病有关，但 MMPs 与人类肾纤维化的组织学关联尚不清楚。
这是一项回顾性研究。获得了机构审查委员会对患者病历、数据分析和病理标本染色的审查批准，豁免了知情同意。对 46 例肾切除患者的 MMP-9 免疫组织化学染色进行了检查，并确定了 MMP-9 在肾纤维化中的表达与肾纤维化的相关性。根据 MMP-9 染色和纤维化评分，将 MMP-9 在单个肾成分中的表达和纤维化分级为高或低。
间质纤维化评分（IFS）和肾小球纤维化评分（GFS）较高的患者血清肌酐水平明显升高，估算肾小球滤过率（eGFR）降低，更有可能患有慢性肾脏病（CKD）和尿路上皮细胞癌。单因素分析表明，IFS 和 GFS 与正常和萎缩肾小管细胞质 MMP-9 表达呈负相关，IFS 与萎缩肾小管核 MMP-9 表达呈正相关。多元逐步回归表明，萎缩肾小管核中 MMP-9 表达（r = 0.4，p = 0.002）是 IFS 的独立预测因子，正常肾小管细胞质中 MMP-9 表达（r = -0.465，p < 0.001）是 GFS 的独立预测因子。
间质纤维化与萎缩肾小管核中 MMP-9 表达相关。我们的结果表明，肾纤维化与正常肾小管细胞质中 MMP-9 表达下降和肾小管萎缩的核中 MMP-9 表达增加有关。
