Pharmacologic inhibiting STAT3 delays the progression of kidney fibrosis in hyperuricemia-induced chronic kidney disease

Aims: Kidney fibrosis is a histological hallmark of chronic kidney disease (CKD), where hyperuricemia is a key independent risk factor. Considerable evidence indicated that STAT3 is one of the crucial signaling pathways in the progression of kidney fibrosis. Here, we investigated that pharmacological blockade of STAT3 delayed the progression of renal fibrosis in hyperuricemia-induced CKD. Main methods: In the study, we used the mixture of adenine and potassium oxonate to perform kidney injury and fibrosis in hyperuricemic mice, accompanied by STAT3 activation in tubular and interstitial cells. Key findings: Treatment with STAT3 inhibitor S3I-201 improved renal dysfunction, reduced serum uric acid level, and delayed the progression of kidney fibrosis. Furthermore, S3I-201 could suppress fibrotic signaling pathway of TGF-beta/Smads, JAK/STAT and NF-Kappa B, as well as inhibit the expression of multiple profibrogenic cytokines/ chemokines in the kidneys of hyperuricemic mice. Significance: These data suggested that STAT3 inhibition was a potent anti-fibrotic strategy in hyperuricemiarelated CKD.

Automated summary

The study demonstrated that the use of STAT3 inhibitor can delay the progression of hyperuricemia-induced CKD renal fibrosis, improve renal function, and lower serum uric acid levels. Additionally, the inhibitor can suppress multiple fibrotic signaling pathways and cytokine expressions.