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| Content Provider | PubMed Central |
|---|---|
| Author | Ding, Yan Kim, Sung Ll Lee, So-young Koo, Ja Kun Wang, Zhibo Choi, Mary E. |
| Copyright Year | 2014 |
| Abstract | Autophagy is an evolutionarily conserved process that cells use to degrade and recycle cellular proteins and remove damaged organelles. During the past decade, there has been a growing interest in defining the basic cellular mechanism of autophagy and its roles in health and disease. However, the functional role of autophagy in kidney fibrosis remains poorly understood. Here, using GFP-LC3 transgenic mice, we show that autophagy is induced in renal tubular epithelial cells (RTECs) of obstructed kidneys after unilateral ureteral obstruction (UUO). Deletion of LC3B (LC3−/− mice) resulted in increased collagen deposition and increased mature profibrotic factor TGF-β levels in obstructed kidneys. Beclin 1 heterozygous (beclin 1+/− ) mice also displayed increased collagen deposition in the obstructed kidneys after UUO. We also show that TGF-β1 induces autophagy in primary mouse RTECs and human renal proximal tubular epithelial (HK-2) cells. LC3 deficiency resulted in increased levels of mature TGF-β in primary RTECs. Under conditions of TGF-β1 stimulation and autoinduction, inhibition of autolysosomal protein degradation by bafilomycin A1 increased mature TGF-β protein levels without alterations in TGF-β1 mRNA. These data suggest a novel intracellular mechanism by which mature TGF-β1 protein levels may be regulated in RTECs through autophagic degradation, which suppresses kidney fibrosis induced by UUO. The dual functions of TGF-β1, as an inducer of TGF-β1 autoinduction and an inducer of autophagy and TGF-β degradation, underscore the multifunctionality of TGF-β1. |
| Related Links | http://dx.doi.org/10.1681/asn.2013101068 |
| Ending Page | 2846 |
| Page Count | 12 |
| Starting Page | 2835 |
| File Format | |
| ISSN | 10466673 |
| e-ISSN | 15333450 |
| Journal | Journal of the American Society of Nephrology : JASN |
| Issue Number | 12 |
| Volume Number | 25 |
| Language | English |
| Publisher | American Society of Nephrology |
| Publisher Date | 2014-12-01 |
| Access Restriction | Open |
| Rights Holder | American Society of Nephrology |
| Subject Keyword | Nephrology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Nephrology |
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