| First Author | Zhang M | Year | 2015 |
| Journal | Cell Death Dis | Volume | 6 |
| Pages | e1847 | PubMed ID | 26247732 |
| Mgi Jnum | J:315401 | Mgi Id | MGI:6830343 |
| Doi | 10.1038/cddis.2015.206 | Citation | Zhang M, et al. (2015) Chop deficiency prevents UUO-induced renal fibrosis by attenuating fibrotic signals originated from Hmgb1/TLR4/NFkappaB/IL-1beta signaling. Cell Death Dis 6:e1847 |
| abstractText | Renal fibrosis, particularly tubulointerstitial fibrosis is considered to be the final manifestation of almost all chronic kidney diseases (CKDs). Herein we demonstrated evidence that CHOP-related ER stress is associated with the development of renal fibrosis in both CKD patients and unilateral ureteral obstruction (UUO)-induced animals, and specifically, mice deficient in Chop were protected from UUO-induced renal fibrosis. Mechanistic studies revealed that loss of Chop protected tubular cells from UUO-induced apoptosis and secondary necrosis along with attenuated Hmgb1 passive release and active secretion. As a result, Chop deficiency suppressed Hmgb1/TLR4/NFkappaB signaling, which then repressed UUO-induced IL-1beta production. Consequently, the IL-1beta downstream Erk1/2 activity and its related c-Jun transcriptional activity were reduced, leading to attenuated production of TGF-beta1 following UUO insult. It was further noted that reduced IL-1beta production also inhibited UUO-induced PI3K/AKT signaling, and both of which ultimately protected mice from UUO-induced renal fibrosis. Together, our data support that suppression of CHOP expression could be a viable therapeutic strategy to prevent renal fibrosis in patients with CKDs. |
