Autophagy activity and expression pattern of autophagy-related markers in the podocytes of patients with lupus nephritis: association with pathological classification

Abstract

Objective: To identify the significance of autophagy in lupus nephritis (LN). Methods: The number of autophagosomes in podocytes was counted and the expression of multiple molecular markers associated with autophagy was evaluated in LN specimens: in renal biopsy specimens from 90 patients with LN and 15 healthy controls, autophagosomes in podocytes were counted using transmission electron microscopy and the expression levels of four autophage related proteins including Beclin-1, microtubule-associated protein light chain 3 (LC3), autophagy-related gene 7 (Atg7), and UNC-51-like kinase 1 (ULK1) were measured using immunohistochemistry. Results: The number of autophagosomes in patients with LN types III, IV, and combined V–IV type were significantly higher than in controls (p < 0.0001; p < 0.0001; p = 0.009, respectively). However, the autophagosomes numbers in patients with II and V types LN were significantly lower than controls (both p < 0.0001). Various levels of marker expression were identified, and they correlated significantly with LN pathology classifications. Moreover, the percentage of marker expression in LN types III, IV and V-IV were significantly higher than controls (p < 0.05), while that in types II and V were lower than controls, although the difference for LC3 and ULK1 was not statistically significant. Conclusions: Autophagy activity and expression pattern of autophagy-related markers in podocytes were significantly positively correlated with LN of types III, IV, and V–IV, but negatively correlated with II and V types. Therefore autophagy could be a useful predictor of LN pathology type, and be informative and helpful in the development of treatment strategies in clinical settings.

Keywords

• autophagy
• podocyte
• beclin-1
• lc3
• atg7
• ulk1