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[Effects of bone morphogenic protein-7 on transdifferentiation and the expression of connective tissue growth factor of human renal tubular epithelial cells induced by transforming growth factor-beta1].
Zhonghua Yi Xue Za Zhi. 2009 Jun 16; 89(23):1639-44.ZY

Abstract

OBJECTIVE

To investigate the effects of bone morphogenic protein (BMP)-7 upon epithelial-to-mesenchymal transition (EMT) and the expression of connective tissue growth factor (CTGF) in human renal proximal tubular epithelial cells (HK-2) induced by transforming growth factor-beta1, (TGF-beta1) and to explore the possible mechanisms of BMP-7 for the inhibition and reversal of renal interstitial fibrosis.

METHODS

HK-2 cells were treated with TGF-beta1 or a combination of TGF-beta1 and BMP-7. RT-PCR and Western blot were used to determine the mRNA and protein expression of alpha-SMA, E-cadherin and CTGF. For EMT reversal experiments, when TGF-beta1-induced EMT occurred, then the medium was removed and replaced with medium containing 200 ng/ml BMP-7. After 48 h, the morphological changes and the expression of E-cadherin were assessed by phase contrast microscopy or immunofluorescent microscopy.

RESULTS

The control cells displayed typical cobblestone morphology of epithelial cells. 3 ng/ml TGF-beta1 induced profound morphologic changes after 48 h, with cells becoming elongated in shape, but addition of 200 ng/ml BMP-7 for 48 h restored the epithelial morphology of HK-2 cells. Indirect immunofluorescence showed that treatment of 3 ng/ml TGF-beta1 resulted in a distinct loss of E-cadherin staining in the plasma membrane of HK-2 cells but subsequent treatment with 200 ng/ml BMP-7 largely restored the E-cadherin protein staining. 3 ng/ml TGF-beta1 significantly up-regulated the mRNA and protein expression of alpha-SMA, reduced the expression of E-cadherin and increased the expression of CTGF after 48 h (vs. control, P < 0.01). BMP-7 dramatically suppressed the mRNA and protein expression of alpha-SMA, restored the expression of E-cadherin and prevented the expression of CTGF in a dose-dependent manner after co-incubation with TGF-beta1 for 48 h (400 ng/ml BMP-7 + TGF-beta1 vs. TGF-beta1, alone, P < 0.01).

CONCLUSIONS

BMP-7 exerts its antifibrotic effect partially through blocking and reversing TGF-beta1-induced EMT and downregulating the expression of CTGF in human renal tubular epithelial cells.

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Publisher Full Text

Authors+Show Affiliations

Xu YF
Department of Nephrology, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
Wan JX
No affiliation info available
Jiang DW
No affiliation info available

MeSH

Bone Morphogenetic Protein 7Cell DifferentiationCell LineCell TransdifferentiationConnective Tissue Growth FactorEpithelial CellsHumansKidney TubulesStromal CellsTransforming Growth Factor beta1

Pub Type(s)

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

Language

chi

PubMed ID

19957515

Citation

Xu, Yan-fang, et al. "[Effects of Bone Morphogenic Protein-7 On Transdifferentiation and the Expression of Connective Tissue Growth Factor of Human Renal Tubular Epithelial Cells Induced By Transforming Growth Factor-beta1]." Zhonghua Yi Xue Za Zhi, vol. 89, no. 23, 2009, pp. 1639-44.
Xu YF, Wan JX, Jiang DW. [Effects of bone morphogenic protein-7 on transdifferentiation and the expression of connective tissue growth factor of human renal tubular epithelial cells induced by transforming growth factor-beta1]. Zhonghua Yi Xue Za Zhi. 2009;89(23):1639-44.
Xu, Y. F., Wan, J. X., & Jiang, D. W. (2009). [Effects of bone morphogenic protein-7 on transdifferentiation and the expression of connective tissue growth factor of human renal tubular epithelial cells induced by transforming growth factor-beta1]. Zhonghua Yi Xue Za Zhi, 89(23), 1639-44.
Xu YF, Wan JX, Jiang DW. [Effects of Bone Morphogenic Protein-7 On Transdifferentiation and the Expression of Connective Tissue Growth Factor of Human Renal Tubular Epithelial Cells Induced By Transforming Growth Factor-beta1]. Zhonghua Yi Xue Za Zhi. 2009 Jun 16;89(23):1639-44. PubMed PMID: 19957515.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Effects of bone morphogenic protein-7 on transdifferentiation and the expression of connective tissue growth factor of human renal tubular epithelial cells induced by transforming growth factor-beta1]. AU - Xu,Yan-fang, AU - Wan,Jian-xin, AU - Jiang,De-wen, PY - 2009/12/5/entrez PY - 2009/12/5/pubmed PY - 2010/2/17/medline SP - 1639 EP - 44 JF - Zhonghua yi xue za zhi JO - Zhonghua Yi Xue Za Zhi VL - 89 IS - 23 N2 - OBJECTIVE: To investigate the effects of bone morphogenic protein (BMP)-7 upon epithelial-to-mesenchymal transition (EMT) and the expression of connective tissue growth factor (CTGF) in human renal proximal tubular epithelial cells (HK-2) induced by transforming growth factor-beta1, (TGF-beta1) and to explore the possible mechanisms of BMP-7 for the inhibition and reversal of renal interstitial fibrosis. METHODS: HK-2 cells were treated with TGF-beta1 or a combination of TGF-beta1 and BMP-7. RT-PCR and Western blot were used to determine the mRNA and protein expression of alpha-SMA, E-cadherin and CTGF. For EMT reversal experiments, when TGF-beta1-induced EMT occurred, then the medium was removed and replaced with medium containing 200 ng/ml BMP-7. After 48 h, the morphological changes and the expression of E-cadherin were assessed by phase contrast microscopy or immunofluorescent microscopy. RESULTS: The control cells displayed typical cobblestone morphology of epithelial cells. 3 ng/ml TGF-beta1 induced profound morphologic changes after 48 h, with cells becoming elongated in shape, but addition of 200 ng/ml BMP-7 for 48 h restored the epithelial morphology of HK-2 cells. Indirect immunofluorescence showed that treatment of 3 ng/ml TGF-beta1 resulted in a distinct loss of E-cadherin staining in the plasma membrane of HK-2 cells but subsequent treatment with 200 ng/ml BMP-7 largely restored the E-cadherin protein staining. 3 ng/ml TGF-beta1 significantly up-regulated the mRNA and protein expression of alpha-SMA, reduced the expression of E-cadherin and increased the expression of CTGF after 48 h (vs. control, P < 0.01). BMP-7 dramatically suppressed the mRNA and protein expression of alpha-SMA, restored the expression of E-cadherin and prevented the expression of CTGF in a dose-dependent manner after co-incubation with TGF-beta1 for 48 h (400 ng/ml BMP-7 + TGF-beta1 vs. TGF-beta1, alone, P < 0.01). CONCLUSIONS: BMP-7 exerts its antifibrotic effect partially through blocking and reversing TGF-beta1-induced EMT and downregulating the expression of CTGF in human renal tubular epithelial cells. SN - 0376-2491 UR - https://www.unboundmedicine.com/medline/citation/19957515/[Effects_of_bone_morphogenic_protein_7_on_transdifferentiation_and_the_expression_of_connective_tissue_growth_factor_of_human_renal_tubular_epithelial_cells_induced_by_transforming_growth_factor_beta1]_ L2 - http://journal.yiigle.com/LinkIn.do?linkin_type=pubmed&amp;issn=0376-2491&amp;year=2009&amp;vol=89&amp;issue=23&amp;fpage=1639 DB - PRIME DP - Unbound Medicine ER -