4.8 Article

Combined glucocorticoid resistance and hyperlactatemia contributes to lethal shock in sepsis

Journal

CELL METABOLISM
Volume 33, Issue 9, Pages 1763-+

Publisher

CELL PRESS
DOI: 10.1016/j.cmet.2021.07.002

Keywords

-

Funding

  1. FWO grant
  2. Agency for Innovation of Science and Technology in Flanders (IWT)
  3. Research Council of Ghent University
  4. Research Foundation Flanders (FWO-Vlaanderen)
  5. FWO Hercules program, Flanders Institute for Biotechnology
  6. Sigrid Juselius Foundation

Ask authors/readers for more resources

Defects in the glucocorticoid receptor signaling pathway exacerbate sepsis pathophysiology by reducing lactate clearance and sensitizing mice to lactate-induced toxicity, ultimately leading to lethal vascular collapse.
Sepsis is a potentially lethal syndrome resulting from a maladaptive response to infection. Upon infection, glucocorticoids are produced as a part of the compensatory response to tolerate sepsis. This tolerance is, however, mitigated in sepsis due to a quickly induced glucocorticoid resistance at the level of the glucocorticoid receptor. Here, we show that defects in the glucocorticoid receptor signaling pathway aggravate sepsis pathophysiology by lowering lactate clearance and sensitizing mice to lactate-induced toxicity. The latter is exerted via an uncontrolled production of vascular endothelial growth factor, resulting in vascular leakage and collapse with severe hypotension, organ damage, and death, all being typical features of a lethal form of sepsis. In conclusion, sepsis leads to glucocorticoid receptor failure and hyperlactatemia, which collectively leads to a lethal vascular collapse.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available