mTOR/p70S6K signaling pathway promotes fibrillin-1 expression in AKI-to-CKD transition post CA/CPR

The possible involvement of mTOR/p70S6K signaling in mediating Fibrillin-1 expression during the transition from acute kidney injury (AKI) to chronic kidney disease (CKD) after cardiac arrest and cardiopulmonary resuscitation (CA/CPR). A CA/CPR AKI model was established using male C57BL/6 mice aged 8–12 weeks. The expression of Fibrillin-1 and activation of the mTOR/p70S6K signaling pathway in kidney tissues were assessed at different time points. Rapamycin, administered intraperitoneally, inhibited the mTOR/p70S6K signaling pathway in CA/CPR AKI mice. Tissue immunofluorescence and immunohistochemistry were used to detect the injury, fibrosis, and inflammatory cell infiltration in renal tissues. The expression level of Fibrillin-1 and components of the mTOR/p70S6K signaling pathway, while ELISA quantified levels of inflammatory factors in renal tissues. Results showed that Fibrillin-1 expression progressively increased alongside enhanced mTOR/p70S6K signaling in the renal tissues of CA/CPR AKI mice. Inhibition of mTOR/p70S6K signaling by rapamycin reduced Fibrillin-1 expression, collagen deposition, and α-SMA levels, alleviating renal injury and decreasing macrophage and T cell infiltration, as well as inflammatory factor production. Conversely, combining rapamycin with Fibrillin-1 overexpression exacerbated renal injury and increased inflammatory factor production. Activation of the mTOR/p70S6K pathway upregulates Fibrillin-1 expression, potentially facilitating the progression from AKI to CKD in CA/CPR mice.