Human umbilical cord mesenchymal stem cell -derived exosomes alleviated the toxic effects induced by lead on HK-2 cells via regulating the unfolded protein response

Lead is an important heavy metal material and also an omnipresent environmental pollutant, which poses extensive hazards to human health, including its nephrotoxicity. However, there are still many unknowns regarding its toxic mechanism and intervention strategy. Here, we revealed that lead exposure promoted the activation of PERK in HK - 2 cells (p - PERK and the ratio of p - PERK / PERK increased), enhanced the expression of its molecular chaperone binding immunoglobulin protein (BIP) and its downstream signaling molecule CCAAT / enhancer - binding protein homologous protein (CHOP). This indicated that lead exposure resulted in the occurrence of the unfolded protein response (UPR) in HK - 2 cells. Further, lead induced significant DNA damage, oxidative stress and apoptosis in HK-2 cells. Especially, when human umbilical cord mesenchymal stem cell - derived exosomes (hucMSC - exos) were ingested by HK-2 cells, all the levels of p - PERK, p - PERK / PERK ratio, BIP and CHOP were significantly down - regulated, which suggested that the UPR was significantly alleviated. Simultaneously, the above-mentioned toxic effects of lead were significantly reduced. Moreover, when GSK2606414 was employed to block the phosphorylation of PERK, the toxic effects of lead were also significantly alleviated. Hence, we conclude that hucMSC - exos can alleviate the toxicity of lead to HK-2 cells via interfering with the UPR, in which PERK plays a crucial role, and it may be a promising target for intervening in the toxicity of lead.