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[Aristolochic acid induced transdifferentiation and apoptosis in human tubular epithelial cells in vitro].
Zhonghua Yu Fang Yi Xue Za Zhi. 2002 Sep; 36(5):301-4.ZY

Abstract

OBJECTIVE

To examine the possible role of aristolochic acid (AA) in transdifferentiation and apoptisis of human tubular epithelial cell line (HKC).

METHODS

Cultured HKC cells were divided into five groups: serum-free (negative control) and treatment with AA at the concentrations of 5 mg/L, 10 mg/L, 20 mg/L and 40 mg/L for 48 hours, respectively. Transdifferentiation of HKC cells was observed with the following methods: detection of the expression of vimentin and cytokeratin of HKC cells with indirect immunoflourescence, determination of expression of E-cadherin and alpha-smooth muscle actin (alpha-SMA) by indirect immunohistochemical double staining, and determination of the proportion of alpha-SMA (+) HKC cells by flow cytometry. The apoptosis of HKC cells was observed with Giemsa staining, TUNEL reaction and agarose gel electrophoresis, and the ratio of apoptotic HKC cells was quantitatively analyzed by flow cytometry with propidium iodide staining.

RESULTS

The expression of cytokeratin and E-cadherin reduced and that of vimentin increased in HKC cells treated with 10 mg/L of AA for 48 hours, and the expression of alpha-SMA (+) in HKC cells treated with 10 mg/L of AA (14.17 +/- 0.61)% was significantly higher than that in serum-free controls (3.57 +/- 0.52)%. Apoptosis of HKC cell treated with 40 mg/L of AA for 48 hours was 53.4%, significantly higher than that in serum-free controls (2%). Treatment with 5 mg/L of AA and 20 mg/L of AA could not induce apoptosis and transdifferentiation of cells.

CONCLUSIONS

Treatment with relatively low concentration of AA (10 mg/L) might induce slight transdifferentiation in cultured HKC cells and that with higher concentration of AA (40 mg/L) for 48 hours might induce apparent apoptosis of these cells, which suggested that transdifferentiation and apoptosis of tubular epithelial cells probably played important roles in aristolochic acid-induced nephropathy.

Authors+Show Affiliations

Division of Nephrology, Peking Union Medical Collage Hospital, Beijing 100730, China.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

chi

PubMed ID

12411187

Citation

Su, Zhen, et al. "[Aristolochic Acid Induced Transdifferentiation and Apoptosis in Human Tubular Epithelial Cells in Vitro]." Zhonghua Yu Fang Yi Xue Za Zhi [Chinese Journal of Preventive Medicine], vol. 36, no. 5, 2002, pp. 301-4.
Su Z, Xu S, Zheng F, et al. [Aristolochic acid induced transdifferentiation and apoptosis in human tubular epithelial cells in vitro]. Zhonghua Yu Fang Yi Xue Za Zhi. 2002;36(5):301-4.
Su, Z., Xu, S., Zheng, F., & Li, Y. (2002). [Aristolochic acid induced transdifferentiation and apoptosis in human tubular epithelial cells in vitro]. Zhonghua Yu Fang Yi Xue Za Zhi [Chinese Journal of Preventive Medicine], 36(5), 301-4.
Su Z, et al. [Aristolochic Acid Induced Transdifferentiation and Apoptosis in Human Tubular Epithelial Cells in Vitro]. Zhonghua Yu Fang Yi Xue Za Zhi. 2002;36(5):301-4. PubMed PMID: 12411187.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Aristolochic acid induced transdifferentiation and apoptosis in human tubular epithelial cells in vitro]. AU - Su,Zhen, AU - Xu,Shaowei, AU - Zheng,Falei, AU - Li,Yan, PY - 2002/11/2/pubmed PY - 2003/7/29/medline PY - 2002/11/2/entrez SP - 301 EP - 4 JF - Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] JO - Zhonghua Yu Fang Yi Xue Za Zhi VL - 36 IS - 5 N2 - OBJECTIVE: To examine the possible role of aristolochic acid (AA) in transdifferentiation and apoptisis of human tubular epithelial cell line (HKC). METHODS: Cultured HKC cells were divided into five groups: serum-free (negative control) and treatment with AA at the concentrations of 5 mg/L, 10 mg/L, 20 mg/L and 40 mg/L for 48 hours, respectively. Transdifferentiation of HKC cells was observed with the following methods: detection of the expression of vimentin and cytokeratin of HKC cells with indirect immunoflourescence, determination of expression of E-cadherin and alpha-smooth muscle actin (alpha-SMA) by indirect immunohistochemical double staining, and determination of the proportion of alpha-SMA (+) HKC cells by flow cytometry. The apoptosis of HKC cells was observed with Giemsa staining, TUNEL reaction and agarose gel electrophoresis, and the ratio of apoptotic HKC cells was quantitatively analyzed by flow cytometry with propidium iodide staining. RESULTS: The expression of cytokeratin and E-cadherin reduced and that of vimentin increased in HKC cells treated with 10 mg/L of AA for 48 hours, and the expression of alpha-SMA (+) in HKC cells treated with 10 mg/L of AA (14.17 +/- 0.61)% was significantly higher than that in serum-free controls (3.57 +/- 0.52)%. Apoptosis of HKC cell treated with 40 mg/L of AA for 48 hours was 53.4%, significantly higher than that in serum-free controls (2%). Treatment with 5 mg/L of AA and 20 mg/L of AA could not induce apoptosis and transdifferentiation of cells. CONCLUSIONS: Treatment with relatively low concentration of AA (10 mg/L) might induce slight transdifferentiation in cultured HKC cells and that with higher concentration of AA (40 mg/L) for 48 hours might induce apparent apoptosis of these cells, which suggested that transdifferentiation and apoptosis of tubular epithelial cells probably played important roles in aristolochic acid-induced nephropathy. SN - 0253-9624 UR - https://www.unboundmedicine.com/medline/citation/12411187/[Aristolochic_acid_induced_transdifferentiation_and_apoptosis_in_human_tubular_epithelial_cells_in_vitro]_ DB - PRIME DP - Unbound Medicine ER -