Abstract: SA-PO312

Autophagy in FOXD1 Stroma-Derived Cells Plays a Critical Role in Renal Tubulointerstitial Fibrosis

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 308 CKD: Mechanisms of Tubulointerstitial Fibrosis

Authors

  • Kim, Yong Kyun, College of Medicine, The Catholic University of Korea, Seoul, Korea (the Republic of)
  • Nam, Sun-ah, The Catholic University of Korea, Seoul, Korea (the Republic of)
  • Yang, Chul Woo, Seoul St. Mary's Hospital, Seoul, Korea (the Republic of)
  • Kim, Jin, The Catholic University of Korea, Seoul, Korea (the Republic of)
Background

Autophagy is a cellular process of degradation of damaged cytoplasmic components and regulates cell death and proliferation. It remians unclear whether the induction of autophagy has positive impact or negative impact in renal tubulointerstitial fibrosis (TIF). FOXD1 lineage pericyte has been recognized to plays a critical role in renal TIF. Here, we hypothesized that autophagy in FOXD1 lineage stromal cell may have pivotal role in renal TIF.

Methods

To examine the distribution of cells where autophagy was induced, we used GFP-LC3 transgenic mice. We also generated conditional knockout mice in which Atg7 is genetically ablated specifically in FOXD1-cells (Atg7f/f;FOXD1-Cre+).

Results

Punctate distribution of GFP-LC3 was was highly expressed in not only renal tubular epithelial cells but interstitial cells after UUO, which were colocalized with PDGFR-β positive cells. Tubulointerstitial fibrosis was enhanced in Atg7f/f;FOXD1-Cre+ after UUO through Smad dependent TGF-β signaling compared with wild type (WT) mice. In Atg7f/f;FOXD1-Cre+, the accumulation of interstitial myofibroblasts was increased and the differentiation of pericyte into myofibroblasts was enhanced compared with WT mice after UUO. The peritubular capillary rarefaction and the apoptosis of interstitial cells were accelerated in Atg7f/f;FOXD1-Cre+ after UUO.

Conclusion

Our data showed that autophagy in FOXD1 stroma-derived cells play a protective role in development of renal TIF, which may be a new therapeutic target for renal TIF.

A. After UUO, GFP-LC3 puncta was highly expressed in not only renal tubular epithelial cells but also interstitial cells, which were colocalized with PDGFR-β positive cells.
B. GFP-LC3 puncta were rarely colocalized with a-SMA–positive interstitial cells or CD31-positive cells.