IMPACT OF TGF-Β/SMAD SIGNALING AND OXIDATIVE STRESS IN RENAL FIBROSIS. IS THERE A LINK? | ||||
| Al-Azhar Journal of Pharmaceutical Sciences | ||||
| Article 3, Volume 61, Issue 1, March 2020, Page 29-45 PDF (1 MB) | ||||
| Document Type: Review Article | ||||
| DOI: 10.21608/ajps.2020.86012 | ||||
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| Author | ||||
| Hamada Sabry Qebesy | ||||
| Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt. | ||||
| Abstract | ||||
| Chronic kidney disease (CKD) has emerged as a major cause of morbidity and mortality worldwide. Irrespective of the cause, renal fibrosis is considered the common final pathway of all kidney diseases driving to end stage renal disease (ESRD). Although some previous studies focused on the involvement of both reactive oxygen species (ROS) and TGF-β/Smad signaling in the development of fibrosis, only few studies highlight on the potential relationship between them in renal fibrosis, so the current study aimed to explore the impact of both ROS and TGF-β/Smad signaling on renal fibrosis on the one hand and to clarify the relationship between them on the other hand, using a mice model of unilateral ureteral obstruction (UUO). Mice were randomized to (n=10/group): sham operated, 3 days ligated, 7 days ligated and 14 days ligated groups. The mice were sacrificed after 3, 7 and 14 days of ligation. Smad3, Smad4 and vimentin were investigated by western blotting while the mRNA level of TGF-β1 was assessed by qRT-PCR. The renal tissue levels of malonaldehyde (MDA), nitric oxide (NO) and reduced glutathione (GSH) besides superoxide dismutase (SOD) activity were assayed calorimetrically. Our immunoblotting results revealed overexpression of Smad3, Smad4 and vimentin in the obstructed kidneys compared to the Sham-operated kidneys. QRT-PCR results, showed TGF-β1 up-regulation coincided with significant disruptions in the oxidant/antioxidant system. In conclusion, our findings revealed that ROS can modulate TGF-β1 signaling through different pathways including Smad pathway. On the other hand, TGF-β1could induce ROS production and inhibit antioxidant system, resulting in redox disturbance. These findings suggest an interesting cycle of TGF- β1 and ROS interplay. | ||||
| Keywords | ||||
| Chronic kidney disease; Renal fibrosis; Unilateral ureteral obstruction; TGF-β1; Smad3; Smad4; Vimentin; Reactive oxygen species | ||||
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