title: Heat shock protein 70 protects rat peritoneal mesothelial cells from advanced glycation end-products-induced epithelial-to-mesenchymal transition through mitogen‑activated protein kinases/extracellular signal-regulated kinases and transforming growth factor-β/Smad pathways.
abstract: 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.
authors: Department of Nephrology, First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors: Jun
authors: J
authors: Yang
authors: Department of Nephrology, First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors: Tiechui
authors: T
authors: Zhu
authors: Department of Nephrology, First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors: Xiangdong
authors: X
authors: Liu
authors: Department of Nephrology, First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors: Lianyun
authors: L
authors: Zhang
authors: Department of Ophthalmology, First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors: Yuxin
authors: Y
authors: Yang
authors: Department of Nephrology, First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors: Jie
authors: J
authors: Zhang
authors: Department of Nephrology, First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors: Minghao
authors: M
authors: Guο
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000199:Actins; D015820:Cadherins; D048049:Extracellular Signal-Regulated MAP Kinases; D017127:Glycation End Products, Advanced; D018840:HSP70 Heat-Shock Proteins; D020928:Mitogen-Activated Protein Kinases; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C498862:Acta2 protein, rat