Unknown

Dataset Information

0

Adrenocorticotropic hormone ameliorates acute kidney injury by steroidogenic-dependent and -independent mechanisms.


ABSTRACT: Adrenocorticotropic hormone (ACTH) has a renoprotective effect in chronic kidney disease; however, its effect on acute kidney injury (AKI) remains unknown. In a rat model of tumor necrosis factor (TNF)-induced AKI, we found that ACTH gel prevented kidney injury, corrected acute renal dysfunction, and improved survival. Morphologically, ACTH gel ameliorated TNF-induced acute tubular necrosis, associated with a reduction in tubular apoptosis. While the steroidogenic response to ACTH gel plateaued, the kidney-protective effect continued to increase at even higher doses, suggesting steroid-independent mechanisms. Of note, ACTH also acts as a key agonist of the melanocortin system, with its cognate melanocortin 1 receptor (MC1R) abundantly expressed in renal tubules. In TNF-injured tubular epithelial cells in vitro, ACTH reinstated cellular viability and eliminated apoptosis. This beneficial effect was blunted in MC1R-silenced cells, suggesting that this receptor mediates the anti-apoptotic signaling of ACTH. Moreover, ACTH gel protected mice against cecal ligation puncture-induced septic AKI better than α-melanocyte-stimulating hormone: a protein equal in biological activity to ACTH except for steroidogenesis. Thus, ACTH has additive renoprotective actions achieved by both steroid-dependent mechanisms and MC1R-directed anti-apoptosis. ACTH may represent a novel therapeutic strategy to prevent or treat AKI.

SUBMITTER: Si J 

PROVIDER: S-EPMC3612362 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC2398767 | biostudies-literature
| S-EPMC7028257 | biostudies-literature
| S-EPMC3857550 | biostudies-literature
| S-EPMC8948942 | biostudies-literature
| S-EPMC6773839 | biostudies-literature
| S-EPMC9526623 | biostudies-literature
| S-EPMC6913588 | biostudies-literature
| S-EPMC5682342 | biostudies-other
| S-EPMC7762132 | biostudies-literature
| S-EPMC6825220 | biostudies-literature