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29, No. 5-6, 2012
Issue release date: June 2012
Section title: Original Paper
Cell Physiol Biochem 2012;29:743-752
(DOI:10.1159/000170949)

Mesangial Medium from IgA Nephropathy Patients Induces Podocyte Epithelial-to-mesenchymal Transition through Activation of the Phosphatidyl Inositol-3-kinase/Akt Signaling Pathway

Wang C.1 · Liu X.1 · Ke ZF.2 · Tang Y.3 · Li C.-C.1 · Li C.-M.1 · Ye Z.C.1 · Zhang J.1 · Lou T.1
1Division of Nephrology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong;2Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong;3Division of Nephrology, Second Affiliated hospital of Sun Yat-Sen University, Guangzhou, Guangdong
email Corresponding Author

Abstract

Background: Podocyte injury plays an important role in glomerulosclerosis in IgA nephropathy (IgAN). Eepithelial-to-mesenchymal transition (EMT) caused by different factors is the main reason for podocyte damage. This study hypothesized that conditioned mesangial medium may induced EMT process of podocytes and thereby lead to glomerular injury or sclerosis. Materials and Methods: Podocytes were incubated in medium from mesangial cells incubated with aggregated IgA1(aIgA1) isolated from IgAN patients. Wortmannin were used to inhibit phosphatidylinositol-3-kinase (PI3-K) in podocytes. Results: Western blot analysis, real-time PCR and confocal fluorescent microscopy demonstrated that reduced expression of P-Cadherin, Zonula occludens-1 (ZO-1) and podocin, increased expression of fibroblast –specific protein (FSP-1), α-smooth muscle action(α-SMA) and desmin in podocytes exposed to medium from mesangial cells incubated with aIgA1 isolated from IgAN patients compared with podocytes cultured in RPMI 1640 medium containing 0.5% fetal bovine serum ( FBS) (p<0.05). Mesangial medium resulted in a greater albumin influx across the podocyte monolayer (p<0.05). Phosphorylation of Akt increased with this medium, as indicated by an increase in the p-Akt/Akt ratio. Treatment with wortmannin partly restored the changes in epithelial and mesenchymal markers and albumin influx. IgAN patients with massive proteinuria showed remarkable α-SMA and FSP-1 expression in podocytes. Conclusion: Our findings indicated that mesangial medium from cells incubated with aIgA1 isolated from IgAN patients induced EMT in podocytes and the PI3-K/ Akt-signaling pathway was involved in the process.

© 2012 S. Karger AG, Basel


  

Key Words

  • IgA1
  • IgA nephropathy
  • Epithelial-to-mesenchymal transition
  • Podocyte
  • Mesangial cell

  

Author Contacts

Tanqi Lou, Division of Nephrology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630 (China), Fax +8620-83856269, E-Mail lou.tq@163.com or wcgz@medmail.com.cn

  

Article Information

Accepted: April 17, 2012
Published online: May 11, 2012
Number of Print Pages : 10

  

Publication Details

Cellular Physiology and Biochemistry (International Journal of Experimental Cellular Physiology, Biochemistry and Pharmacology)

Vol. 29, No. 5-6, Year 2012 (Cover Date: June 2012)

Journal Editor: Guggino W. (Baltimore, Md.), Lang F. (Tübingen)
ISSN: 1015-8987 (Print), eISSN: 1421-9778 (Online)

For additional information: http://www.karger.com/CPB


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Background: Podocyte injury plays an important role in glomerulosclerosis in IgA nephropathy (IgAN). Eepithelial-to-mesenchymal transition (EMT) caused by different factors is the main reason for podocyte damage. This study hypothesized that conditioned mesangial medium may induced EMT process of podocytes and thereby lead to glomerular injury or sclerosis. Materials and Methods: Podocytes were incubated in medium from mesangial cells incubated with aggregated IgA1(aIgA1) isolated from IgAN patients. Wortmannin were used to inhibit phosphatidylinositol-3-kinase (PI3-K) in podocytes. Results: Western blot analysis, real-time PCR and confocal fluorescent microscopy demonstrated that reduced expression of P-Cadherin, Zonula occludens-1 (ZO-1) and podocin, increased expression of fibroblast –specific protein (FSP-1), α-smooth muscle action(α-SMA) and desmin in podocytes exposed to medium from mesangial cells incubated with aIgA1 isolated from IgAN patients compared with podocytes cultured in RPMI 1640 medium containing 0.5% fetal bovine serum ( FBS) (p<0.05). Mesangial medium resulted in a greater albumin influx across the podocyte monolayer (p<0.05). Phosphorylation of Akt increased with this medium, as indicated by an increase in the p-Akt/Akt ratio. Treatment with wortmannin partly restored the changes in epithelial and mesenchymal markers and albumin influx. IgAN patients with massive proteinuria showed remarkable α-SMA and FSP-1 expression in podocytes. Conclusion: Our findings indicated that mesangial medium from cells incubated with aIgA1 isolated from IgAN patients induced EMT in podocytes and the PI3-K/ Akt-signaling pathway was involved in the process.

© 2012 S. Karger AG, Basel


  

Author Contacts

Tanqi Lou, Division of Nephrology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630 (China), Fax +8620-83856269, E-Mail lou.tq@163.com or wcgz@medmail.com.cn

  

Article Information

Accepted: April 17, 2012
Published online: May 11, 2012
Number of Print Pages : 10

  

Publication Details

Cellular Physiology and Biochemistry (International Journal of Experimental Cellular Physiology, Biochemistry and Pharmacology)

Vol. 29, No. 5-6, Year 2012 (Cover Date: June 2012)

Journal Editor: Guggino W. (Baltimore, Md.), Lang F. (Tübingen)
ISSN: 1015-8987 (Print), eISSN: 1421-9778 (Online)

For additional information: http://www.karger.com/CPB


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Accepted: 4/17/2012
Published online: 5/11/2012
Issue release date: June 2012

Number of Print Pages: 10
Number of Figures: 0
Number of Tables: 0

ISSN: 1015-8987 (Print)
eISSN: 1421-9778 (Online)

For additional information: http://www.karger.com/CPB


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.