Hypoxia causes important changes of extracellular matrix biomarkers and ADAMTS proteinases in the adriamycin-induced renal fibrosis model.

AIM: Renal fibrosis is a common cause of renal dysfunction with chronic kidney diseases. This process is characterized by excessive production of extracellular matrix (ECM) or inhibition of ECM degradation. ADAMTS proteinases, which are widely presented in mammals, have very critical roles in ECM remodeling. We aimed to study the role of ADAMTS proteinases and some of the ECM markers in the pathogenesis of renal fibrosis, and to investigate the effects of hypoxia upon these biomarkers.

METHODS: In addition to the control group, adriamycin (ADR) treated rats were divided into 4 groups as ADR, sham, and two hypoxia groups. Renal nephropathy was assessed biochemical assays, pathological and immunohistochemical staining methods. The expression of ADAMTSs and mRNA were determined using Western blotting and real-time PCR, respectively.

RESULTS: Renal dysfuntion and tissue damage in favor of ECM accumulation and renal fibrosis were observed in the ADR group. This was approved by remarkable changes in the expression of ADAMTS such as increased ADAMTS-1, -12 and -15. In addition, it was found that hypoxia and duration of hypoxia enhanced markers of tubulointerstitial fibrosis in the rat kidney tissues. Also expression differences especially in ADAMTS-1, -6 and -15 were observed in the hypoxia groups. The variable and different expression pattern of ADAMTS proteinases in the ADR-induced renal fibrosis suggest that ADAMTS family members are involved in the development and progression of fibrosis.

CONCLUSION: Our findings show that the hypoxia promotes development of renal fibrosis. ADAMTS proteases may provide some important signals in contributing with the early diagnosis and treatment options of renal fibrosis. This article is protected by copyright. All rights reserved.