Cyclin G1 and TASCC regulate kidney epithelial cell G₂-M arrest and fibrotic maladaptive repair.

ABSTRACT: Fibrosis contributes to the progression of chronic kidney disease (CKD). Severe acute kidney injury can lead to CKD through proximal tubular cell (PTC) cycle arrest in the G₂-M phase, with secretion of profibrotic factors. Here, we show that epithelial cells in the G₂-M phase form target of rapamycin (TOR)-autophagy spatial coupling compartments (TASCCs), which promote profibrotic secretion similar to the senescence-associated secretory phenotype. Cyclin G1 (CG1), an atypical cyclin, promoted G₂-M arrest in PTCs and up-regulated TASCC formation. PTC TASCC formation was also present in humans with CKD. Prevention of TASCC formation in cultured PTCs blocked secretion of profibrotic factors. PTC-specific knockout of a key TASCC component reduced the rate of ki

SUBMITTER: Canaud G 

PROVIDER: S-EPMC6527117 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature