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Epithelial‑to‑mesenchymal transition (EMT) may result in damage to the peritoneum and the development of fibrosis in peritoneal mesothelial cells (PMCs). However, the mechanism underlying EMT in peritoneal mesothelial cells is not well understood. Heat shock proteins (HSPs) were initially identified as proteins that are expressed following exposure of cells to environmental stress. However, their function in the development of EMT in PMCs remains to be fully elucidated. In the present study, the effect of HSP70 on advanced glycation end‑products (AGEs)‑induced EMT in peritoneal mesothelial cells was investigated by overexpression of this protein using a plasmid and knockdown of HSP70 using small interfering RNA. In addition, the underlying molecular mechanisms were explored. The results demonstrated that AGEs activated changes associated with EMT, including the loss of E‑cadherin and the increase in α‑smooth muscle actin. Furthermore, AGEs also induced the upregulation of HSP70, which led to the partial inhibition of EMT in PMCs. HSP70 inhibits EMT by modulating transforming growth factor‑β (TGF‑β)/Smad expression and the mitogen‑activated protein kinases (MAPK)/extracellular signal‑regulated kinases (ERK) signaling pathways. The findings suggested that HSP70 augments the cellular defense capacity through inhibition of TGF‑β/Smad and MAPK/ERK signaling pathways, thereby protecting PMCs from AGEs‑induced EMT.

Renal tubular epithelial cells can enter the epithelial‑to‑mesenchymal transition (EMT) in response to chronic hypoxia. EMT is a process which involves the phenotypic conversion of epithelial cells, that is believed to have an important role in renal fibrosis. However, the underlying mechanisms of the involvement of EMT in renal fibrosis remain to be elucidated. Adrenomedullin (AMD) has been implicated in renal fibrosis and is induced by hypoxia. The aims of the present study were to determine whether ADM signaling was active in human proximal tubular epithelial cells cultured under hypoxic conditions, and to observe the activity of ADM during EMT. The expression levels of ADM were significantly increased, in a time‑dependent manner, in HK‑2 and HKC human proximal tubular epithelial cells, cultured under hypoxic conditions. Overexpression of exogenous ADM was accompanied by increased expression levels of the epithelial markers E‑cadherin and tight junction protein‑1, and decreased expression levels of the mesenchymal markers vimentin and α‑smooth muscle actin, during hypoxia. Knock‑down of ADM expression by small hairpin RNA, or co‑administration of an ADM peptide inhibitor, in HK‑2 cells significantly exacerbated hypoxia‑induced EMT, as compared to the lack of effect observed in the untransfected controls. ADM was shown to suppress EMT by inhibiting the activation of extracellular signal‑regulated kinase (ERK), and this effect was prevented by the ERK activator apigenin. The results of the present study suggest that ADM has an important role in promoting EMT in hypoxic human proximal tubular epithelial cells. ADM may therefore represent a novel therapeutic target in the treatment of injured kidneys.