The protective role of Agrin and CAF22 in hypertensive nephropathy

Background: Hypertensive nephropathy (HN), a major complication of hypertension, is characterized by key pathological features such as renal inflammation and fibrosis. Recent studies have demonstrated that Agrin plays a significant role in tissues such as the heart and skeletal muscle. Its cleavage product, the C-terminal Agrin fragment 22 (CAF22), has been suggested as a potential new biomarker for renal insufficiency. However, the role of Agrin and CAF22 in the HN remains underexplored.

Methods: C57BL/6 mice were implanted with micro-osmotic pumps for continuous, slow infusion of angiotensin II (Ang II) over 4 weeks to establish a model of HN. Two weeks after pump implantation, recombinant Agrin (rAgrin) was administered via tail vein injection for 2 weeks. In vitro, rAgrin and recombinant CAF22 (rCAF22) were used to treat Ang II-stimulated renal tubular epithelial cells.

Results: Agrin expression was remarkedly upregulated in the renal tissues of HN mice. RAgrin treatment effectively alleviated renal fibrosis, mitigated pathological changes, and preserved renal function by inhibiting NF-κB pathway activation and reducing inflammatory cytokines production. Similarly, rCAF22 similarly inhibited renal inflammation and fibrosis. Elevated serum CAF22 levels were observed in patients with renal insufficiency and hypertension, as well as in HN mice.

Conclusion: Both rAgrin and rCAF22 exert protective effects against renal inflammation and fibrosis in HN. Moreover, CAF22 may serve as a promising biomarker for the diagnosis of HN.

Agrin; Angiotensin II; CAF22; Fibrosis; Hypertensive nephropathy; Inflammation.