Functional role of pyruvate kinase M2 in cell cycle arrest and extracellular matrix secretion of renal tubular epithelial cell induced by transforming growth factor-β1
Objective To explore the functional role of pyruvate kinase M2（PKM 2） in cell cycle arrest and extracellular matrix secretion of renal tubular epithelial cell induced by transforming growth factor-β1（TGF-β1）.Methods HK-2 cells were stimulated by TGF-β1 for establishing an in vitro model of renal tub...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | zho |
| Published: |
Editorial Department of Journal of Clinical Nephrology
2021-01-01
|
| Series: | Linchuang shenzangbing zazhi |
| Subjects: | |
| Online Access: | http://www.lcszb.com/thesisDetails?columnId=57902018&Fpath=home&index=0 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849323526191841280 |
|---|---|
| author | Wu Hong-luan An Ning Chen Xiao-cui Pang Hao-wen Yang Chen Liu Hua-feng |
| author_facet | Wu Hong-luan An Ning Chen Xiao-cui Pang Hao-wen Yang Chen Liu Hua-feng |
| author_sort | Wu Hong-luan |
| collection | DOAJ |
| description | Objective To explore the functional role of pyruvate kinase M2（PKM 2） in cell cycle arrest and extracellular matrix secretion of renal tubular epithelial cell induced by transforming growth factor-β1（TGF-β1）.Methods HK-2 cells were stimulated by TGF-β1 for establishing an in vitro model of renal tubulointerstitial fibrosis.The function of dimeric PKM2 was suppressed by a PKM2 allosteric agent TEPP-46 or its antagonist shikonin.The expressions of fibronectin, collagen I and connective tissue growth factor（CTGF） were detected by Western blot.The ratio of HK-2 cells in cycle phase was performed by propidium iodide staining and analyzed by flow cytometry.Also the expression of cell cycle inhibitor p21 was detected by Western blot.Results As compared with control-treated cells, a treatment of TGF-β1 significantly boosted the levels of extracellular matrix fibronectin, collagen I,pro-fibrotic CTGF and dimeric PKM2.By contrast, TEPP-46 or shikonin markedly suppressed the elevations of fibronectin, collagen I and CTGF.Moreover, an inhibition of dimeric PKM2 by TEPP-46 or shikonin remarkably suppressed the proportion of TGF-β1-treated HK-2 cells in G1 phase through a down-regulation of p21.Conclusion Dimeric PKM2 promotes cell cycle arrest and extracellular matrix secretion of renal tubular epithelial cell induced by TGF-β1.And targeting dimeric PKM2 may represent a novel therapeutic strategy for delaying the progression of renal tubulointerstitial fibrosis. |
| format | Article |
| id | doaj-art-e7f3cc5750ba4b9faffbab8be6a9eda9 |
| institution | Kabale University |
| issn | 1671-2390 |
| language | zho |
| publishDate | 2021-01-01 |
| publisher | Editorial Department of Journal of Clinical Nephrology |
| record_format | Article |
| series | Linchuang shenzangbing zazhi |
| spelling | doaj-art-e7f3cc5750ba4b9faffbab8be6a9eda92025-08-20T03:49:02ZzhoEditorial Department of Journal of Clinical NephrologyLinchuang shenzangbing zazhi1671-23902021-01-01211009101457902018Functional role of pyruvate kinase M2 in cell cycle arrest and extracellular matrix secretion of renal tubular epithelial cell induced by transforming growth factor-β1Wu Hong-luanAn NingChen Xiao-cuiPang Hao-wenYang ChenLiu Hua-fengObjective To explore the functional role of pyruvate kinase M2（PKM 2） in cell cycle arrest and extracellular matrix secretion of renal tubular epithelial cell induced by transforming growth factor-β1（TGF-β1）.Methods HK-2 cells were stimulated by TGF-β1 for establishing an in vitro model of renal tubulointerstitial fibrosis.The function of dimeric PKM2 was suppressed by a PKM2 allosteric agent TEPP-46 or its antagonist shikonin.The expressions of fibronectin, collagen I and connective tissue growth factor（CTGF） were detected by Western blot.The ratio of HK-2 cells in cycle phase was performed by propidium iodide staining and analyzed by flow cytometry.Also the expression of cell cycle inhibitor p21 was detected by Western blot.Results As compared with control-treated cells, a treatment of TGF-β1 significantly boosted the levels of extracellular matrix fibronectin, collagen I,pro-fibrotic CTGF and dimeric PKM2.By contrast, TEPP-46 or shikonin markedly suppressed the elevations of fibronectin, collagen I and CTGF.Moreover, an inhibition of dimeric PKM2 by TEPP-46 or shikonin remarkably suppressed the proportion of TGF-β1-treated HK-2 cells in G1 phase through a down-regulation of p21.Conclusion Dimeric PKM2 promotes cell cycle arrest and extracellular matrix secretion of renal tubular epithelial cell induced by TGF-β1.And targeting dimeric PKM2 may represent a novel therapeutic strategy for delaying the progression of renal tubulointerstitial fibrosis.http://www.lcszb.com/thesisDetails?columnId=57902018&Fpath=home&index=0Renal tubular epithelial cellPyruvate kinase M2TGF-β1Cell cycle arrestExtracellular matrix secretion |
| spellingShingle | Wu Hong-luan An Ning Chen Xiao-cui Pang Hao-wen Yang Chen Liu Hua-feng Functional role of pyruvate kinase M2 in cell cycle arrest and extracellular matrix secretion of renal tubular epithelial cell induced by transforming growth factor-β1 Linchuang shenzangbing zazhi Renal tubular epithelial cell Pyruvate kinase M2 TGF-β1 Cell cycle arrest Extracellular matrix secretion |
| title | Functional role of pyruvate kinase M2 in cell cycle arrest and extracellular matrix secretion of renal tubular epithelial cell induced by transforming growth factor-β1 |
| title_full | Functional role of pyruvate kinase M2 in cell cycle arrest and extracellular matrix secretion of renal tubular epithelial cell induced by transforming growth factor-β1 |
| title_fullStr | Functional role of pyruvate kinase M2 in cell cycle arrest and extracellular matrix secretion of renal tubular epithelial cell induced by transforming growth factor-β1 |
| title_full_unstemmed | Functional role of pyruvate kinase M2 in cell cycle arrest and extracellular matrix secretion of renal tubular epithelial cell induced by transforming growth factor-β1 |
| title_short | Functional role of pyruvate kinase M2 in cell cycle arrest and extracellular matrix secretion of renal tubular epithelial cell induced by transforming growth factor-β1 |
| title_sort | functional role of pyruvate kinase m2 in cell cycle arrest and extracellular matrix secretion of renal tubular epithelial cell induced by transforming growth factor β1 |
| topic | Renal tubular epithelial cell Pyruvate kinase M2 TGF-β1 Cell cycle arrest Extracellular matrix secretion |
| url | http://www.lcszb.com/thesisDetails?columnId=57902018&Fpath=home&index=0 |
| work_keys_str_mv | AT wuhongluan functionalroleofpyruvatekinasem2incellcyclearrestandextracellularmatrixsecretionofrenaltubularepithelialcellinducedbytransforminggrowthfactorb1 AT anning functionalroleofpyruvatekinasem2incellcyclearrestandextracellularmatrixsecretionofrenaltubularepithelialcellinducedbytransforminggrowthfactorb1 AT chenxiaocui functionalroleofpyruvatekinasem2incellcyclearrestandextracellularmatrixsecretionofrenaltubularepithelialcellinducedbytransforminggrowthfactorb1 AT panghaowen functionalroleofpyruvatekinasem2incellcyclearrestandextracellularmatrixsecretionofrenaltubularepithelialcellinducedbytransforminggrowthfactorb1 AT yangchen functionalroleofpyruvatekinasem2incellcyclearrestandextracellularmatrixsecretionofrenaltubularepithelialcellinducedbytransforminggrowthfactorb1 AT liuhuafeng functionalroleofpyruvatekinasem2incellcyclearrestandextracellularmatrixsecretionofrenaltubularepithelialcellinducedbytransforminggrowthfactorb1 |