FK228 recovers thiram-induced tibial dyschondroplasia in chicken via hypoxia inducible factor-1α.

Tibial dyschondroplasia (TD) is a disease of many avian species characterized by an enlarged and avascular lesion in the proximal tibiotarsal bone. The aim of present study was to evaluate the effects of hypoxia-inducible factor-1α(HIF-1α) inhibition on thiram- induced TD using synthetic medicine FK228 and the association between HIF-1α and heat-shock protein 90 (Hsp90). One hundred and fifty broiler chicks were equally divided into 3 groups: control; thiram fed; and FK228 treatment. Expressions of HIF-1α and Hsp90 genes were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR) on day 10 and 14 post-hatch. Western blot analysis of HIF-1α and Hsp90 gene was performed to measure the protein levels at the end of the experiment. Results showed that HIF-1α and Hsp90 levels were significantly (P less than 0.05) up-regulated in the thiram group as compared to the control group. Meanwhile, FK228 (HIF-1α inhibitor) significantly (P less than 0.05) down- regulated the mRNA and protein levels of HIF-1α and Hsp90, restored the size of growth plate and diminished lameness. In conclusion, HIF-1α and Hsp90 play an important role in the formation of avascular growth plate and there is a direct relationship between HIF-1α and Hsp90 for the progression of TD pathogenesis. Therefore, HIF- 1α may prevent and control TD in broiler chickens.