Cdc42-interacting protein 4 silencing relieves pulmonary fibrosis in STZ-induced diabetic mice via the Wnt/GSK-3β/β-catenin pathway

- Expression of CIP4 is up-regulated in STZ-induced diabetic mice.
- Silencing of CIP4 inhibits PF in STZ-induced diabetic mice.
- Silencing of CIP4 inhibits EMT in STZ-induced diabetic mice.
- CIP4 silencing protects diabetic PF mice through the Wnt/GSK-3β/β-catenin pathway.

Cdc42-interacting protein-4 (CIP4) has been reported to be closely associated with diabetic nephropathy in rat. However, little is known about the correlation between CIP4 and diabetic pulmonary fibrosis (PF) in mice. Here, diabetes was induced by streptozotocin (STZ), and later lung tissue was collected and subjected to hematoxylin and eosin (H & E) staining for morphological examination. The distinct up-regulation of CIP4 was observed in diabetic PF mice. CIP4 silencing increased overall weight and decreased lung weight. Simultaneously, levels of TGF-β1, collagen-1, collagen-3 and hydroxyproline were down-regulated by CIP4 silencing, accompanied by an increase in MMP-9 expression and a decrease in TIMP-1 expression. Down-regulation of CIP4 suppressed EMT by decreasing the expression of vimentin and α-SMA as well as augmenting E-cadherin expression. Mechanistic analysis confirmed that CIP4 silencing inhibited p-GSK-3β and β-catenin expression, indicating that CIP4 down-regulation attenuated the activation of Wnt/GSK-3β/β-catenin signaling. However, β-catenin overexpression ameliorated the inhibitory effect of CIP4 down-regulation on lung tissue damage, fibrosis-related cytokines and EMT. These results suggest that CIP4 silencing can efficiently alleviate STZ-induced PF in mice, perhaps through suppressing Wnt/GSK-3β/β-catenin signaling.

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