Osteopontin mediating cyclosporine A induced epithelial‐to‐mesenchymal transition on rat renal tubular epithelial cells

Xu, Danfeng; Chen, Xia; Deng, Zhaohong; Tan, Ruoyun; Liu, Chao; Lu, Pei-Hua; Zhang, Wei; Gu, Min

doi:10.1002/cbin.10149

Cited by 3 publications

(3 citation statements)

References 19 publications

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“…It attracts macrophages and participates in the development of renal fibrosis after kidney injury [14], [33]. Our results are consistent with previous data indicating that osteopontin contributes to chronic CsA-induced nephrotoxicity by recruiting macrophages, triggering epithelial-mesenchymal transition in renal tubular epithelial cells and promoting tubulointerstitial fibrosis [11], [34].…”

Section: Discussionsupporting

confidence: 92%

Predictive Usefulness of Urinary Biomarkers for the Identification of Cyclosporine A-Induced Nephrotoxicity in a Rat Model

et al. 2014

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The main side effect of cyclosporine A (CsA), a widely used immunosuppressive drug, is nephrotoxicity. Early detection of CsA-induced acute nephrotoxicity is essential for stop or minimize kidney injury, and timely detection of chronic nephrotoxicity is critical for halting the drug and preventing irreversible kidney injury. This study aimed to identify urinary biomarkers for the detection of CsA-induced nephrotoxicity. We allocated salt-depleted rats to receive CsA or vehicle for 7, 14 or 21 days and evaluated renal function and hemodynamics, microalbuminuria, renal macrophage infiltration, tubulointerstitial fibrosis and renal tissue and urinary biomarkers for kidney injury. Kidney injury molecule-1 (KIM-1), tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), fibronectin, neutrophil gelatinase-associated lipocalin (NGAL), TGF-β, osteopontin, and podocin were assessed in urine. TNF-α, IL-6, fibronectin, osteopontin, TGF-β, collagen IV, alpha smooth muscle actin (α -SMA) and vimentin were assessed in renal tissue. CsA caused early functional renal dysfunction and microalbuminuria, followed by macrophage infiltration and late tubulointerstitial fibrosis. Urinary TNF-α, KIM-1 and fibronectin increased in the early phase, and urinary TGF-β and osteopontin increased in the late phase of CsA nephrotoxicity. Urinary biomarkers correlated consistently with renal tissue cytokine expression. In conclusion, early increases in urinary KIM-1, TNF-α, and fibronectin and elevated microalbuminuria indicate acute CsA nephrotoxicity. Late increases in urinary osteopontin and TGF-β indicate chronic CsA nephrotoxicity. These urinary kidney injury biomarkers correlated well with the renal tissue expression of injury markers and with the temporal development of CsA nephrotoxicity.

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Section: Discussionsupporting

confidence: 92%

Predictive Usefulness of Urinary Biomarkers for the Identification of Cyclosporine A-Induced Nephrotoxicity in a Rat Model

et al. 2014

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“…Besides, OPN in the study by Kashiwagi et al . was shown to have an impact on the expression of transforming growth factor (TGF)‐β1 and the number of macrophages, and interestingly, TGF‐β1 treatment could increase OPN in rat renal epithelial cell line (NRK‐52E) in a dose‐dependent manner . Therefore, it is natural to suppose that the up‐regulation of HOTAIR in RIF might be due to the TGF‐β‐induced production of OPN.…”

Section: Discussionmentioning

confidence: 99%

LncRNA HOTAIR promotes renal interstitial fibrosis by regulating Notch1 pathway via the modulation of miR‐124

et al. 2019

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“…It is considered that NGAL is involved in favorable regeneration of renal tubules after injury, whereas OPN expressing in incomplete regeneration of renal epithelia participates in renal progressive fibrosis via type 2 EMT. In fact, the addition of OPN to NRK-52E induces EMT [ 81 ]. However, there is a report describing that NGAL may participate in type 3 EMT in carcinoma with metastasis [ 82 , 83 ], an opposite phenomenon to type 2 EMT in renal fibrosis.…”

Section: Pathogenesis Of Type 2 Epithelial To Mesenchymal Transitimentioning

confidence: 99%

Pathogenesis of Type 2 Epithelial to Mesenchymal Transition (EMT) in Renal and Hepatic Fibrosis

Tennakoon

Izawa

Kuwamura

et al. 2015

JCM

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Epithelial to mesenchymal transition (EMT), particularly, type 2 EMT, is important in progressive renal and hepatic fibrosis. In this process, incompletely regenerated renal epithelia lose their epithelial characteristics and gain migratory mesenchymal qualities as myofibroblasts. In hepatic fibrosis (importantly, cirrhosis), the process also occurs in injured hepatocytes and hepatic progenitor cells (HPCs), as well as ductular reaction-related bile epithelia. Interestingly, the ductular reaction contributes partly to hepatocarcinogenesis of HPCs, and further, regenerating cholangiocytes after injury may be derived from hepatic stellate cells via mesenchymal to epithelia transition, a reverse phenomenon of type 2 EMT. Possible pathogenesis of type 2 EMT and its differences between renal and hepatic fibrosis are reviewed based on our experimental data.

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Osteopontin mediating cyclosporine A induced epithelial‐to‐mesenchymal transition on rat renal tubular epithelial cells

Cited by 3 publications

References 19 publications

Predictive Usefulness of Urinary Biomarkers for the Identification of Cyclosporine A-Induced Nephrotoxicity in a Rat Model

Predictive Usefulness of Urinary Biomarkers for the Identification of Cyclosporine A-Induced Nephrotoxicity in a Rat Model

LncRNA HOTAIR promotes renal interstitial fibrosis by regulating Notch1 pathway via the modulation of miR‐124

Pathogenesis of Type 2 Epithelial to Mesenchymal Transition (EMT) in Renal and Hepatic Fibrosis

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