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Article: Mesenchymal stem cells modulate albumin-induced renal tubular inflammation and fibrosis.

TitleMesenchymal stem cells modulate albumin-induced renal tubular inflammation and fibrosis.
Authors
Issue Date2014
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
PLoS One, 2014, v. 9 n. 3, article no. e90883 How to Cite?
AbstractBone marrow-derived mesenchymal stem cells (BM-MSCs) have recently shown promise as a therapeutic tool in various types of chronic kidney disease (CKD) models. However, the mechanism of action is incompletely understood. As renal prognosis in CKD is largely determined by the degree of renal tubular injury that correlates with residual proteinuria, we hypothesized that BM-MSCs may exert modulatory effects on renal tubular inflammation and epithelial-to-mesenchymal transition (EMT) under a protein-overloaded milieu. Using a co-culture model of human proximal tubular epithelial cells (PTECs) and BM-MSCs, we showed that concomitant stimulation of BM-MSCs by albumin excess was a prerequisite for them to attenuate albumin-induced IL-6, IL-8, TNF-alpha, CCL-2, CCL-5 overexpression in PTECs, which was partly mediated via deactivation of tubular NF-kappaB signaling. In addition, albumin induced tubular EMT, as shown by E-cadherin loss and alpha-SMA, FN and collagen IV overexpression, was also prevented by BM-MSC co-culture. Albumin-overloaded BM-MSCs per se retained their tri-lineage differentiation capacity and overexpressed hepatocyte growth factor (HGF) and TNFalpha-stimulating gene (TSG)-6 via P38 and NF-kappaB signaling. Albumin-induced tubular CCL-2, CCL-5 and TNF-alpha overexpression were suppressed by recombinant HGF treatment, while the upregulation of alpha-SMA, FN and collagen IV was attenuated by recombinant TSG-6. Neutralizing HGF and TSG-6 abolished the anti-inflammatory and anti-EMT effects of BM-MSC co-culture in albumin-induced PTECs, respectively. In vivo, albumin-overloaded mice treated with mouse BM-MSCs had markedly reduced BUN, tubular CCL-2 and CCL-5 expression, alpha-SMA and collagen IV accumulation independent of changes in proteinuria. These data suggest anti-inflammatory and anti-fibrotic roles of BM-MSCs on renal tubular cells under a protein overloaded condition, probably mediated via the paracrine action of HGF and TSG-6.
Persistent Identifierhttp://hdl.handle.net/10722/203060
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorWu, HJen_US
dc.contributor.authorYiu, WHen_US
dc.contributor.authorLi, RXen_US
dc.contributor.authorWong, DWLen_US
dc.contributor.authorLeung, JCKen_US
dc.contributor.authorChan, LYYen_US
dc.contributor.authorZhang, Yen_US
dc.contributor.authorLian, Qen_US
dc.contributor.authorLin, Men_US
dc.contributor.authorTse, HFen_US
dc.contributor.authorLai, KNen_US
dc.contributor.authorTang, SCWen_US
dc.date.accessioned2014-09-19T11:29:24Z-
dc.date.available2014-09-19T11:29:24Z-
dc.date.issued2014en_US
dc.identifier.citationPLoS One, 2014, v. 9 n. 3, article no. e90883en_US
dc.identifier.issn1932-6203-
dc.identifier.urihttp://hdl.handle.net/10722/203060-
dc.description.abstractBone marrow-derived mesenchymal stem cells (BM-MSCs) have recently shown promise as a therapeutic tool in various types of chronic kidney disease (CKD) models. However, the mechanism of action is incompletely understood. As renal prognosis in CKD is largely determined by the degree of renal tubular injury that correlates with residual proteinuria, we hypothesized that BM-MSCs may exert modulatory effects on renal tubular inflammation and epithelial-to-mesenchymal transition (EMT) under a protein-overloaded milieu. Using a co-culture model of human proximal tubular epithelial cells (PTECs) and BM-MSCs, we showed that concomitant stimulation of BM-MSCs by albumin excess was a prerequisite for them to attenuate albumin-induced IL-6, IL-8, TNF-alpha, CCL-2, CCL-5 overexpression in PTECs, which was partly mediated via deactivation of tubular NF-kappaB signaling. In addition, albumin induced tubular EMT, as shown by E-cadherin loss and alpha-SMA, FN and collagen IV overexpression, was also prevented by BM-MSC co-culture. Albumin-overloaded BM-MSCs per se retained their tri-lineage differentiation capacity and overexpressed hepatocyte growth factor (HGF) and TNFalpha-stimulating gene (TSG)-6 via P38 and NF-kappaB signaling. Albumin-induced tubular CCL-2, CCL-5 and TNF-alpha overexpression were suppressed by recombinant HGF treatment, while the upregulation of alpha-SMA, FN and collagen IV was attenuated by recombinant TSG-6. Neutralizing HGF and TSG-6 abolished the anti-inflammatory and anti-EMT effects of BM-MSC co-culture in albumin-induced PTECs, respectively. In vivo, albumin-overloaded mice treated with mouse BM-MSCs had markedly reduced BUN, tubular CCL-2 and CCL-5 expression, alpha-SMA and collagen IV accumulation independent of changes in proteinuria. These data suggest anti-inflammatory and anti-fibrotic roles of BM-MSCs on renal tubular cells under a protein overloaded condition, probably mediated via the paracrine action of HGF and TSG-6.-
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action-
dc.relation.ispartofPLoS Oneen_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleMesenchymal stem cells modulate albumin-induced renal tubular inflammation and fibrosis.en_US
dc.typeArticleen_US
dc.identifier.emailWu, HJ: hjwu@hku.hken_US
dc.identifier.emailYiu, WH: whyiu@hku.hken_US
dc.identifier.emailLeung, JCK: jckleung@hku.hken_US
dc.identifier.emailChan, LYY: yychanb@hku.hken_US
dc.identifier.emailZhang, Y: zyl1999@hkucc.hku.hken_US
dc.identifier.emailLian, Q: qzlian@hkucc.hku.hken_US
dc.identifier.emailTse, HF: hftse@hkucc.hku.hken_US
dc.identifier.emailLai, KN: knlai@hku.hken_US
dc.identifier.emailTang, SCW: scwtang@hku.hken_US
dc.identifier.authorityLeung, JCK=rp00448en_US
dc.identifier.authorityLian, Q=rp00267en_US
dc.identifier.authorityTse, HF=rp00428en_US
dc.identifier.authorityLai, KN=rp00324en_US
dc.identifier.authorityTang, SCW=rp00480en_US
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0090883-
dc.identifier.pmid24646687-
dc.identifier.pmcidPMC3960109-
dc.identifier.hkuros235358en_US
dc.identifier.volume9en_US
dc.identifier.issue3en_US
dc.publisher.placeUnited States-

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