Kidney Week

Abstract: TH-PO830

Podocyte Autophagy Could Protect Renal Injury in Lupus and Might Be a Therapeutic Target

Session Information

• Glomerular Diseases: Immunology and Inflammation - I
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1202 Glomerular Diseases: Immunology and Inflammation

Authors

• Zhou, Xujie, Peking University First Hospital, Beijing, China

Xujie Zhou,

• Qi, Yuan-yuan, 1. Renal Division, Peking University First Hospital, 2. Peking University Institute of Nephrology,, Beijing, BeiJIng, China

Yuan-yuan Qi,

• Yanna, Wang, Peking University First Hospital, Beijing, China

Wang Yanna,

• Zhang, Hong, Peking University First Hospital, Beijing, China

Hong Zhang,

Background

More recent studies suggested that defects in autophagy contribute to the pathogenesis of SLE, especially in adaptive immunity. Occurrence and progression of lupus nephritis (LN) is the end result of complex interactions between regulation of immune responses and pathological process by renal resident cells, but there is still a lot of missing information for an establishment on the role of autophagy in pathogenesis of LN and as a therapy target.

Methods

Systemic and organ specific etiologies of autophagy were firsly evaluated by autophagy protein quantification in tissue homogenates in MRL^lpr/lpr lupus prone and female C57BL mice. Analysis of gene expression was also adopted in human blood and urine sediments. Then, some key mediators of the disease, including complement inactivated serum, IgG from patients with LN (IgG-LN) and IFN-α were chosen to induce podocyte autophagy. Podocyte injuries including apoptosis, podocin derangement, albumin filtration, and wound healing were monitered simultaneously with autophagy steady-state and flux.

Results

Elevated LC3B in kidney homogenates and increased autophagosomes in podocyte from MRL^lpr/lpr were observed. In humans, mRNA levels of some key autophagy genes were increased in blood and urinary sediments, and podocyte autophagosomes were observed in renal biopsies from patients with LN. Complement inactivated serum, IgG-LN and IFN-α could induce podocyte autophagy in a time and dosage dependent manner, and by reactive oxygen species production and mTORC1 inhibition, respectively. Autophagy inhibition aggravated podocyte damage whereas its inducer relieved the injury.

Conclusion

Podocyte autophagy could protect renal injury in lupus and might be a therapeutic target.

Funding

• Government Support - Non-U.S.