The pro-apoptotic and pro-inflammatory effects of FK506 binding protein 5 (FKBP5) in sepsis-induced acute kidney injury have been previously reported. However, its biological functions and underlying mechanisms in regulating sepsis-induced intestinal injury remain elusive. Therefore, this study aimed to explore the effects of FKBP5 on sepsis-induced intestinal injury.
Methods:
A mouse model of sepsis was established by cecal ligation and puncture (CLP). A cell model was established by treating Caco-2 cells with lipopolysaccharide (LPS). The impacts of FKBP5 knockdown on apoptosis, barrier integrity, inflammation, and the nuclear factor kappa B (NF-κB) signaling were evaluated in ileal tissue and Caco-2 cells.
Results:
FKBP5 expression was elevated in the ileal tissue in response to CLP and LPS treatments. In mice with sepsis, FKBP5 knockdown reduced cell apoptosis and regulated Bax, Bcl-2, and cleaved PARP levels. FKBP5 knockdown also reduced the levels of D-lactic acid, tumor necrosis factor alpha, interleukin (IL)-6, and IL-1β, improved intestinal histopathological damage, and enhanced the expression of zonula occludens-1 and occludin. FKBP5 knockdown also displayed protective effects in LPS-stimulated cells. FKBP5 knockdown inhibited the NF-κB signaling in CLP and LPS groups.
Conclusion:
Inhibition of FKBP5 alleviates inflammation and intestinal barrier dysfunction in sepsis, partially by inhibiting the NF-κB signaling.
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