Extracellular HSP60 triggers tissue regeneration and wound healing by regulating inflammation and cell proliferation.

Pei, Wuhong; Tanaka, Katsuya; Huang, Sunny C; Xu, Lisha; Liu, Baoying; Sinclair, Jason; Idol, Jennifer; Varshney, Gaurav K et al. · NPJ Regen Med · 2016

basic_science · Level V

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Abstract

After injury, zebrafish can restore many tissues that do not regenerate well in mammals, making it a useful vertebrate model for studying regenerative biology. We performed a systematic screen to identify genes essential for hair cell regeneration in zebrafish, and found that the heat shock protein Hspd1 (Hsp60) has a critical role in the regeneration of hair cells and amputated caudal fins. We showed HSP60-injected extracellularly promoted cell proliferation and regeneration in both hair cells and caudal fins. We showed that <i>hspd1</i> mutant was deficient in leukocyte infiltration at the site of injury. Topical application of HSP60 in a diabetic mouse skin wound model dramatically accelerated wound healing compared with controls. Stimulation of human peripheral blood mononuclear cells with HSP60 triggered a specific induction of M2 phase CD163-positive monocytes. Our results demonstrate that the normally intracellular chaperonin HSP60 has an extracellular signalling function in injury inflammation and tissue regeneration, likely through promoting the M2 phase for macrophages.