Year: 2025
Type: dissertation
Abstract: Kidney fibrosis, a major complication of chronic kidney disease, is marked by excessive extracellular matrix deposition, inflammation, and fibrotic transformation of renal cells. Commonly driven by diabetes and hypertension, it lacks curative treatment, with current options significantly impairing quality of life and imposing an economic burden. This underscores the need for novel therapeutic targets. Tubular cells play a key role in the development of fibrosis, as upon injury, they start to release cytokines that contribute to inflammation and fibrosis. Rho family small GTPases are key mediators of tubular cytokine release, and RhoB levels are known to increase in the urine of kidney disease patients. However, the regulation and role of RhoB in kidney disease remain unknown. We hypothesized that Angiotensin II (ANG II) and TNF-α upregulate RhoB expression in tubular epithelial cells via NADPH oxidase (NOX) and/or ERK signalling pathways. To assess this, cultured kidney epithelial cells were treated with ANG II or TNF-α, and RhoB expression was assessed by Western blotting. Specific inhibitors were used to evaluate the involvement of ERK and NOX. Both ANG II and TNF-α upregulated RhoB. Inhibition of ERK or NOX paradoxically increased basal RhoB levels, suggesting these pathways may suppress basal RhoB expression. Further, neither inhibitor altered the effect of ANG II or TNFα on RhoB. In conclusion, ANG II and TNF-α induce RhoB independently of NOX and ERK, warranting further mechanistic exploration.
Source: TSpace (University of Toronto)
Author: Emmanuel, Olanike Mercy
Institution: University of Toronto
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7132862258