Peptide FK2 attenuates inflammation and pro-fibrotic cellular transitions via targeting the IKKβ/NF-κB/TGF-β1 axis in renal fibrosis.

Chronic kidney disease (CKD) refers to a pathological change characterized by the progressive and irreversible loss of renal function. Renal fibrosis is the final pathological outcome of CKD without effective treatment. Persistent inflammation is one of the most important factors in the occurrence and development of fibrosis. FK2, a 9-amino-acid-residue peptide originating from the silk of Zea mays L., was reported to have anti-inflammatory effects on mice. In this study, we verified for the first time that FK2 has an inhibitory effect on the process of renal fibrosis both in vivo and in vitro. Mechanistically, we identified IKKβ as a direct target of FK2. By binding to IKKβ, FK2 concurrently suppresses the IKKβ/NF-κB and TGF-β1/Smad2/3 signaling axes, thereby effectively mitigating the associated inflammatory response and key cellular processes including macrophage-to-myofibroblast transition (MMT) and epithelial-mesenchymal transition (EMT). Our research provides a promising candidate molecule for the development of anti-renal fibrosis drugs, and targeting IKKβ presents a viable strategy for treating kidney fibrosis.