Choi Sung-Eun, Jeon Nara, Choi Hoon Young, Shin Jae Il, Jeong Hyeon Joo, Lim Beom Jin
Department of Pathology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
Mol Med Rep. 2017 Sep;16(3):2477-2482. doi: 10.3892/mmr.2017.6918. Epub 2017 Jul 4.
Tubulointerstitial fibrosis is a common end point of chronic kidney diseases, and preventing its progression is key to avoiding renal failure. Transforming growth factor‑β (TGF‑β) and associated molecules promote tubulointerstitial fibrosis; however, effective therapies targeting these molecules have yet to be developed. Lysyl oxidase‑like 2 (LOXL2), which is involved in invasive growth and metastasis of malignant neoplasms, has recently been reported to serve a key role in hepatic and pulmonary fibrosis. However, little is currently known regarding LOXL2 expression in the kidney and its involvement in tubulointerstitial fibrosis. The present study evaluated LOXL2 expression in human and mouse kidney tissues, as well as in cultured renal cells. LOXL2 protein expression was detected in glomerular capillary loops and tubular epithelial cells in human and mouse kidneys. Glomerular LOXL2 was localized to the cytoplasm of podocytes, as determined by double immunofluorescence microscopy using a podocyte marker (synaptopodin). This result was supported by western blot analysis, which demonstrated that LOXL2 protein expression is present in cultured human podocytes and HK‑2 human proximal tubular cells. In addition, the mRNA and protein expression levels of LOXL2 were higher in a mouse model of tubulointerstitial fibrosis compared with in control mice. In addition, immunohistochemistry results demonstrated that LOXL2 is present in the fibrous interstitium and infiltrating mononuclear cells in a mouse model of tubulointerstitial fibrosis. The present study demonstrated that LOXL2 is expressed in compartments of renal tissue, where it appears to contribute to the progression of tubulointerstitial fibrosis.
肾小管间质纤维化是慢性肾脏病常见的终点结局，预防其进展是避免肾衰竭的关键。转化生长因子-β（TGF-β）及相关分子可促进肾小管间质纤维化；然而，针对这些分子的有效治疗方法尚未开发出来。赖氨酰氧化酶样2（LOXL2）参与恶性肿瘤的侵袭性生长和转移，最近有报道称其在肝纤维化和肺纤维化中起关键作用。然而，目前对于LOXL2在肾脏中的表达及其在肾小管间质纤维化中的作用知之甚少。本研究评估了LOXL2在人及小鼠肾脏组织以及培养的肾细胞中的表达。在人及小鼠肾脏的肾小球毛细血管袢和肾小管上皮细胞中检测到了LOXL2蛋白表达。通过使用足细胞标志物（突触素）的双重免疫荧光显微镜检查确定，肾小球LOXL2定位于足细胞的细胞质中。蛋白质印迹分析支持了这一结果，该分析表明LOXL2蛋白表达存在于培养的人足细胞和HK-2人近端肾小管细胞中。此外，与对照小鼠相比，在肾小管间质纤维化小鼠模型中LOXL2的mRNA和蛋白表达水平更高。此外，免疫组织化学结果表明，在肾小管间质纤维化小鼠模型中，LOXL2存在于纤维间质和浸润的单核细胞中。本研究表明，LOXL2在肾组织各部分表达，似乎在肾小管间质纤维化进展中发挥作用。
