Fibrosis is a common phenotype that often leads to the progression of blood pressure-induced
chronic kidney disease (CKD).
TGF-beta plays an important role in promoting pathogenesis, and NLRP3 is a critical mediator in the progression of blood pressure-induced CKD. However, the pathophysiological roles of the
TGF-beta-mediated NLRP3 pathway in modulating
fibrosis in blood pressure-induced CKD have not been elucidated. The present study aims to investigate the contribution of
TGF-beta-mediated NLRP3
inflammasome to renal
fibrosis in rats with
high blood pressure. By treating rats with
angiotensin II (Ang II) for 14 days, we observed the development of
fibrosis, characterized by epithelial-mesenchymal transition (EMT) markers [alpha-smooth muscle actin (alpha-SMA), MMP-2, and
MMP-9]. Immunohistochemical analysis further revealed that
TGF-beta and NLRP3
inflammasome activation [high-mobility group box 1 (
HMGB1), IL-1beta, and NLRP3] were significantly upregulated in the kidney of rats with Ang II-induced
hypertension. Interestingly, we observed that Ang II could not increase the production of NLRP3
proteins, but
TGF-beta could induce
NLRP3 protein expression in cultured NRK-52E cells. Furthermore, we speculated that
TGF-beta played a pathogenic role in Ang II-induced CKD because
TGF-beta induced the activation of NLRP3
inflammasomes and Gasdermin D cleavage expression. We also proved that the pharmacological inhibition of NLRP3 by ISO caused a decrease in
TGF-beta-induced NLRP3
inflammasome activation and the expression of EMT markers (alpha-SMA and CollagenI) and Gasdermin D cleavage. Collectively, these results suggest that
TGF-beta-mediated NLRP3
inflammasome activation may cause the release of
HMGB1 and an increase in Gasdermin D cleavage in NRK-52E, thereby contributing to renal
fibrosis in Ang II-induced CKD. These findings provide novel insights into the pathogenic role of NLRP3 in CKD associated with
high blood pressure.