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The role of the p38 MAPK signaling pathway in high glucose-induced epithelial-mesenchymal transition of cultured human renal tubular epithelial cells.
PLoS One. 2011; 6(7):e22806.Plos

Abstract

BACKGROUND

Epithelial-mesenchymal transition of tubular epithelial cells, which is characterized by a loss of epithelial cell characteristics and a gain of ECM-producing myofibroblast characteristics, is an essential mechanism that is involved in tubulointerstitial fibrosis, an important component of the renal injury that is associated with diabetic nephropathy. Under diabetic conditions, p38 MAPK activation has been reported in glomeruli and mesangial cells; however, studies on p38 MAPK in TECs are lacking. In this study, the role of p38 MAPK in AP-1 activation and in the EMT in the human proximal tubular epithelial cell line (HK-2) under high glucose concentration conditions is investigated.

METHODOLOGY/PRINCIPAL FINDINGS

A vector for small interfering RNA that targets p38 MAPK was constructed; the cells were then either transfected with p38 siRNA or pretreated with a chemical inhibitor of AP-1 and incubated with low glucose plus TGF-β1 or high glucose for 48 h. Cells that were not transfected or pretreated and were exposed to low glucose with or without TGF-β1 or high glucose for 48 h were considered to be the controls. We found that high glucose induced an increase in TGF-β1. And high glucose-induced p38 MAPK activation was inhibited by p38 siRNA (P<0.05). A significant decline in E-cadherin and CK expression and a notable increase in vimentin and α-SMA were detected when exposed to low glucose with TGF-β1 or high glucose, and a significant raise of secreted fibronectin were detected when exposed to high glucose; whereas these changes were reversed when the cells were treated with p38 siRNA or AP-1 inhibitor (P<0.05). AP-1 activity levels and Snail expression were up-regulated under high glucose conditions but were markedly down-regulated through knockdown of p38 MAPK with p38 siRNA or pretreatment with AP-1 inhibitor (P<0.05).

CONCLUSION

This study suggests that p38 MAPK may play an important role in the high glucose-induced EMT by activating AP-1 in tubular epithelial cells.

Authors+Show Affiliations

Department of Nephrology, Provincial Hospital Affliated to Shandong University, JiNan, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21829520

Citation

Lv, Zhi-Mei, et al. "The Role of the P38 MAPK Signaling Pathway in High Glucose-induced Epithelial-mesenchymal Transition of Cultured Human Renal Tubular Epithelial Cells." PloS One, vol. 6, no. 7, 2011, pp. e22806.
Lv ZM, Wang Q, Wan Q, et al. The role of the p38 MAPK signaling pathway in high glucose-induced epithelial-mesenchymal transition of cultured human renal tubular epithelial cells. PLoS ONE. 2011;6(7):e22806.
Lv, Z. M., Wang, Q., Wan, Q., Lin, J. G., Hu, M. S., Liu, Y. X., & Wang, R. (2011). The role of the p38 MAPK signaling pathway in high glucose-induced epithelial-mesenchymal transition of cultured human renal tubular epithelial cells. PloS One, 6(7), e22806. https://doi.org/10.1371/journal.pone.0022806
Lv ZM, et al. The Role of the P38 MAPK Signaling Pathway in High Glucose-induced Epithelial-mesenchymal Transition of Cultured Human Renal Tubular Epithelial Cells. PLoS ONE. 2011;6(7):e22806. PubMed PMID: 21829520.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of the p38 MAPK signaling pathway in high glucose-induced epithelial-mesenchymal transition of cultured human renal tubular epithelial cells. AU - Lv,Zhi-Mei, AU - Wang,Qun, AU - Wan,Qiang, AU - Lin,Jian-Gong, AU - Hu,Meng-Si, AU - Liu,You-Xia, AU - Wang,Rong, Y1 - 2011/07/29/ PY - 2011/01/14/received PY - 2011/07/07/accepted PY - 2011/8/11/entrez PY - 2011/8/11/pubmed PY - 2011/12/13/medline SP - e22806 EP - e22806 JF - PloS one JO - PLoS ONE VL - 6 IS - 7 N2 - BACKGROUND: Epithelial-mesenchymal transition of tubular epithelial cells, which is characterized by a loss of epithelial cell characteristics and a gain of ECM-producing myofibroblast characteristics, is an essential mechanism that is involved in tubulointerstitial fibrosis, an important component of the renal injury that is associated with diabetic nephropathy. Under diabetic conditions, p38 MAPK activation has been reported in glomeruli and mesangial cells; however, studies on p38 MAPK in TECs are lacking. In this study, the role of p38 MAPK in AP-1 activation and in the EMT in the human proximal tubular epithelial cell line (HK-2) under high glucose concentration conditions is investigated. METHODOLOGY/PRINCIPAL FINDINGS: A vector for small interfering RNA that targets p38 MAPK was constructed; the cells were then either transfected with p38 siRNA or pretreated with a chemical inhibitor of AP-1 and incubated with low glucose plus TGF-β1 or high glucose for 48 h. Cells that were not transfected or pretreated and were exposed to low glucose with or without TGF-β1 or high glucose for 48 h were considered to be the controls. We found that high glucose induced an increase in TGF-β1. And high glucose-induced p38 MAPK activation was inhibited by p38 siRNA (P<0.05). A significant decline in E-cadherin and CK expression and a notable increase in vimentin and α-SMA were detected when exposed to low glucose with TGF-β1 or high glucose, and a significant raise of secreted fibronectin were detected when exposed to high glucose; whereas these changes were reversed when the cells were treated with p38 siRNA or AP-1 inhibitor (P<0.05). AP-1 activity levels and Snail expression were up-regulated under high glucose conditions but were markedly down-regulated through knockdown of p38 MAPK with p38 siRNA or pretreatment with AP-1 inhibitor (P<0.05). CONCLUSION: This study suggests that p38 MAPK may play an important role in the high glucose-induced EMT by activating AP-1 in tubular epithelial cells. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/21829520/The_role_of_the_p38_MAPK_signaling_pathway_in_high_glucose_induced_epithelial_mesenchymal_transition_of_cultured_human_renal_tubular_epithelial_cells_ L2 - http://dx.plos.org/10.1371/journal.pone.0022806 DB - PRIME DP - Unbound Medicine ER -