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Updated: Jan 30, 2026
Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations
Published on: September 17, 2012
Cyclin G1 and TASCC regulate kidney epithelial cell G2-M arrest and fibrotic maladaptive repair
Guillaume Canaud1,2,3, Craig R Brooks1,4, Seiji Kishi1,5
1Renal Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
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 kidney fibrosis progression in mice with CKD. CG1 induction and TASCC formation also occur in liver fibrosis. Deletion of CG1 reduced G2-M phase cells and TASCC formation in vivo. This study provides mechanistic evidence supporting how profibrotic G2-M arrest is induced in kidney injury and how G2-M-arrested PTCs promote fibrosis, identifying new therapeutic targets to mitigate kidney fibrosis.
Insights
Severe kidney injury causes cell cycle arrest, promoting fibrosis. Targeting Cyclin G1 (CG1) and TOR-autophagy spatial coupling compartments (TASCCs) may prevent this kidney fibrosis progression.
Area of Science:
- Nephrology
- Cell Biology
- Molecular Medicine
Background:
- Fibrosis is a key driver of chronic kidney disease (CKD) progression.
- Severe acute kidney injury can lead to CKD via proximal tubular cell (PTC) G2-M phase cell cycle arrest and profibrotic factor secretion.
Purpose of the Study:
- To investigate the mechanisms linking G2-M cell cycle arrest in PTCs to kidney fibrosis.
- To identify potential therapeutic targets for mitigating kidney fibrosis.
Main Methods:
- Investigated the role of Cyclin G1 (CG1) and TOR-autophagy spatial coupling compartments (TASCCs) in PTCs.
- Utilized cell culture models and PTC-specific knockout mice with induced CKD.
- Examined TASCC formation and profibrotic factor secretion in relation to CG1 levels and G2-M arrest.
Main Results:
- Epithelial cells in G2-M phase form TASCCs, promoting profibrotic secretion.
- CG1 induces G2-M arrest in PTCs and upregulates TASCC formation, observed in human CKD.
- Preventing TASCC formation inhibited profibrotic secretion; PTC-specific TASCC component knockout reduced fibrosis progression in mice.
- CG1 induction and TASCC formation were also observed in liver fibrosis.
Conclusions:
- Mechanistic link established between profibrotic G2-M arrest, TASCCs, and kidney fibrosis.
- CG1 and TASCCs are key mediators of G2-M-arrested PTCs promoting fibrosis.
- CG1 and TASCCs represent potential therapeutic targets for kidney fibrosis treatment.
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