Background
Despite lack of clinical therapy in acute kidney injury (AKI) or its progression to chronic kidney disease (CKD), administration of growth factors shows great potential in the treatment of renal repair and further fibrosis. At early phase of AKI, administration of exogenous fibroblast growth factor 2 (FGF2) protects against renal injury by inhibition of mitochondrial damage and inflammatory response. Here, we investigated whether this treatment attenuates the long-term renal interstitial fibrosis induced by I/R injury.
Methods
Unilateral renal ischemia-reperfusion (I/R) with contralateral nephrectomy was utilized as an in vivo model for AKI and subsequent CKD. Rats were randomly divided into four groups: Sham-operation group, I/R group, I/R-FGF2 group and FGF2-3D group. These groups were monitored for up to 2 months. Serum creatinine, inflammatory response and renal histopathology changes were detected to evaluate the role of FGF2 in AKI and followed renal interstitial fibrosis. Moreover, the expression of vimentin, α-SMA, CD31 and CD34 were examined.
Results
Two months after I/R injury, the severity of renal interstitial fibrosis was significantly attenuated in both of I/R-FGF2 group and FGF2-3D group, compared with I/R group. The protective effects of FGF2 administration were associated with the reduction of high-mobility group box 1 (HMGB1) mediated inflammatory response, the inhibition of TGF-β1/Smads signaling induced epithelial-mesenchymal transition and the maintenance of peritubular capillary structure.
Conclusions
A single dose of exogenous FGF2 administration 1 hour or 3 days after reperfusion inhibited renal fibrogenesis and thus blocked the transition of AKI to CKD. Our findings provided novel insight into the role of FGF signaling in AKI to CKD progression and underscored potential of FGF based therapy for this devastating disease.
Acute kidney injury (AKI) and renal interstitial fibrosis are global clinical syndromes associated with high morbidity and mortality. Renal ischemia-reperfusion (I/R) injury, which commonly occurs during surgery, is one of the major causes of AKI. Nevertheless, an efficient therapeutic approach for AKI and the development of renal interstitial fibrosis is still lacking due to its elusive pathogenetic mechanism. Here, we showed that chitosan oligosaccharide (COS), a natural oligomer polysaccharide degraded from chitosan, significantly attenuates I/R-induced AKI and maintains glomerular filtration function by inhibiting oxidative stress, mitochondrial damage, and excessive endoplasmic reticulum stress both
in vitro
and
in vivo
. In addition, long-term administration of COS can also attenuate the proliferation of myofibroblasts, mitigate extra cellular matrix deposition, and thus inhibit the transition of AKI to chronic kidney disease through participating in metabolic and redox biological processes. Our findings provide novel insights into the protective role of COS against acute kidney injury.
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