Correlation Engine 2.0
Clear Search sequence regions


  • adenovirus (1)
  • BCL2 (1)
  • BNIP3 (3)
  • E1B (1)
  • gene knockdown (1)
  • HIF- 1 (7)
  • hypoxia (4)
  • mice (1)
  • renal fibrosis (9)
  • target gene (1)
  • Sizes of these terms reflect their relevance to your search.

    The molecular basis of renal interstitial fibrosis, a major pathological feature of progressive kidney diseases, remains poorly understood. Autophagy has been implicated in renal fibrosis, but whether it promotes or inhibits fibrosis remains controversial. Moreover, it is unclear how autophagy is activated and sustained in renal fibrosis. The present study was designed to address these questions using the in vivo mouse model of unilateral ureteral obstruction and the in vitro model of hypoxia in renal tubular cells. Both models showed the activation of hypoxia-inducible factor-1 (HIF-1) and autophagy along with fibrotic changes. Inhibition of autophagy with chloroquine reduced renal fibrosis in unilateral ureteral obstruction model, whereas chloroquine and autophagy-related gene 7 knockdown decreased fibrotic changes in cultured renal proximal tubular cells, supporting a profibrotic role of autophagy. Notably, pharmacological and genetic inhibition of HIF-1 led to the suppression of autophagy and renal fibrosis in these models. Mechanistically, knock down of BCL2 and adenovirus E1B 19-kDa-interacting protein 3 (BNIP3), a downstream target gene of HIF, decreased autophagy and fibrotic changes during hypoxia in BUMPT cells. Together, these results suggest that HIF-1 may activate autophagy via BNIP3 in renal tubular cells to facilitate the development of renal interstitial fibrosis.NEW & NOTEWORTHY Autophagy has been reported to participate in renal fibrosis, but its role and underlying activation mechanism is unclear. In this study, we report the role of HIF-1 in autophagy activation in models of renal fibrosis and further investigate the underlying mechanism.

    Citation

    Jing Liu, Man J Livingston, Guie Dong, Qingqing Wei, Ming Zhang, Shuqin Mei, Jiefu Zhu, Chun Zhang, Zheng Dong. HIF-1 contributes to autophagy activation via BNIP3 to facilitate renal fibrosis in hypoxia in vitro and UUO in vivo. American journal of physiology. Cell physiology. 2024 Mar 01;326(3):C935-C947

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 38284121

    View Full Text