Effects of proteasome inhibitors on rat renal fibrosis in vitro and in vivo

Abstract

Proteasome inhibitors attenuate TGF-β signalling by blocking Smad signal transduction in vitro, but do not inhibit renal interstitial fibrosis in vivo.

Crosstalk between autophagy and proteasome protein degradation systems: possible implications for cancer therapy

“…Recent experimental and clinical data have shown that proteasome inhibitors serve as a new and promising class of anticancer agents [21,24,77,79,84,87,144]. However, the data presented in this review proved beyond doubt that proteasome inhibition induces www.fhc.viamedica.pl autophagy in the majority of cells.…”

Original article Nigrostriatal pathway degeneration in rats after intraperitoneal administration of proteasome inhibitor MG-132

“…The study revealed that MG-132 is not an adequate treatment to prevent endotoxin-induced diaphragmatic dysfunction [20,42] but partially prevents muscle atrophy associated with disuse [20]. MG-132 administered in relatively large doses (4 mg/kg, repeated seven times) did not ameliorate tubulointerstitial fibrosis in rat unilateral ureteral obstruction [37]. Positive effects of MG-132, namely attenuation pneumonitis and cytokine gene expression in vivo by reducing coronavirus were observed [28].…”

“…Authors more often indicate a possible systemic toxic effect and even an increase in the mortality risk in the reports where there were late effects of MG-132 and the effects of multiple doses of the MG-132 studied [29,37]. A dose of 10 mg/kg of body weight (cumulative dose of above 30 mg/kg) provided intraperitoneally seems to lead to high mortality, although rats can survive a cumulative dose of 105 mg/kg [7] delivered in 14 doses during seven days subcutaneously.…”

“…In a low dose (0.1 mg/kg) MG-132 administered intraperitoneally once per day even for 2 or 8 weeks may effectively prevent cardiac remodelling and dysfunction in pressure-overloaded hearts without marked drug toxicity [29]. The effects of intraperitoneal injection of MG-132 was also studied on urinary [37], musculoskeletal [20,42], and respiratory systems [28]. The study revealed that MG-132 is not an adequate treatment to prevent endotoxin-induced diaphragmatic dysfunction [20,42] but partially prevents muscle atrophy associated with disuse [20].…”

Bence-Jones Protein λ-type Multiple Myeloma Patient Withdrawn from Maintenance Hemodialysis after Long-term Bortezomib and Dexamethasone Therapy

“…In addition, bortezomib ameliorated liver fibrosis with a significant reduction of the α-smooth muscle actin expression in a N-nitrosodiethylamine-induced liver fibrosis rat model (16). In a renal in vitro investigation, MG132 (an experimental proteasome inhibiting agent) blocked the TGFβ-induced transformation of renal fibroblast NRK49F cells to myofibroblast cells (17), which express extracellular matrix and α-smooth muscle actin and play a key role in the progression of renal fibrosis (18). These preclinical observations support our hypothesis that bortezomib ameliorated the subsequent renal fibrosis in the present case.…”