Lysyl oxidase-like 2 is expressed in kidney tissue and is associated with the progression of tubulointerstitial fibrosis
نویسندگان
چکیده
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.
منابع مشابه
Semicarbazide-sensitive amine oxidase and kidney disease.
With better understanding of the molecular mechanisms underpinning chronic kidney disease, the roles of inflammation and fibrosis are becoming increasingly inseparable. The progression of renal disease is characterized by pathomorphological changes that consist of early inflammatory responses followed by tubulointerstitial fibrosis, tubular atrophy, and glomerular and vascular sclerosis. Curren...
متن کاملOmega-3 fatty acid supplementation attenuates oxidative stress, inflammation, and tubulointerstitial fibrosis in the remnant kidney.
Significant reduction of renal mass initiates a series of hemodynamic and nonhemodynamic events which lead to proteinuria, glomerulosclerosis, tubulointerstitial injury, and end-stage renal failure. Lipid mediators derived from fatty acids participate in regulation of renal hemodynamic and nonhemodynamic processes that influence progression of renal disease. Composition of cellular fatty acids ...
متن کاملEvaluation of Therapeutic Effects of Autologous Bone Marrow Mesenchymal Stem Cells to Prevent the Progression of Chronic Nephropathy in Renal Transplant
Background Chronic allograft nephropathy(CAN) is one of the most common causes of chronic and end stage renal disease. It is defined with Mainly tubular atrophy and interstitial fibrosis and no evidence of any other etiology, or functional disorder that caused at least three months after transplantation . Control of risk factors (HTN,DM,HLP, …) and limiting usage of calcineurin inhibitors...
متن کاملLysyl oxidase-like 2 represses Notch1 expression in the skin to promote squamous cell carcinoma progression.
Lysyl oxidase-like 2 (LOXL2) is involved in a wide range of physiological and pathological processes, including fibrosis and tumor progression, implicating intracellular and extracellular functions. To explore the specific in vivo role of LOXL2 in physiological and tumor contexts, we generated conditional gain- and loss-of-function mouse models. Germ-line deletion of Loxl2 promotes lethality in...
متن کاملPlatelet-derived growth factors (PDGFs) in glomerular and tubulointerstitial fibrosis
Renal fibrosis is the hallmark of chronic kidney disease progression and is characterized by an exaggerated wound-healing process with the production of renal scar tissue. It comprises both the glomerular and the tubulointerstitial compartments. Among the factors that contribute to kidney fibrosis, the members of the platelet-derived growth factor (PDGF) family are among the best characterized ...
متن کامل