Faculty Opinions recommendation of Glycerol-3-phosphate is an FGF23 regulator derived from the injured kidney.

Tanshinone IIA is a diterpene extracted from Salvia miltiorrhiza, a popular and safe herb medicine that has been widely used in China and other Asian countries. Previous studies have demonstrated the pleiotropic effects of Tanshinone IIA on many disease treatments via its antitoxicity, anti-inflammation, anti-oxidative stress, as well as antifibrosis activities. However, its effect on acute kidney injury (AKI) has not been fully investigated. Here, we show for the first time that systemic administration of Tanshinone IIA can lead to improved kidney function in folic acid-induced kidney injury mice. In the acute phase of AKI, Tanshinone IIA attenuated renal tubular epithelial injury, as determined by histologic changes and the detection of Neutrophil gelatinase-associated lipocalin (NGAL) in the kidney and urine. Additionally, Tanshinone IIA treatment resulted in elevated proliferating cell nuclear antigen (PCNA) expression and decreased inflammatory cells infiltration as well as chemokine expression, suggesting that Tanshinone IIA promoted renal repair following AKI and inhibited local inflammatory response in the injured kidney. This led to decreased long-term fibrosis in the injured kidney, characterized by less accumulation of fibronectin and collagen I in tubulointerstitium. Taken together, these results suggest that Tanshinone IIA may represent a potential approach for AKI treatment.

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Hemizygous deletion of CTGF/CCN2 does not suffice to prevent fibrosis of the severely injured kidney

Matrix Biology ◽

10.1016/j.matbio.2012.06.002 ◽

2012 ◽

Vol 31 (7-8) ◽

pp. 421-431 ◽

Cited By ~ 18

Author(s):

Lucas L. Falke ◽

Amélie Dendooven ◽

Jan Willem Leeuwis ◽

Tri Q. Nguyen ◽

Rob J. van Geest ◽

...

Keyword(s):

Severely Injured ◽

Hemizygous Deletion ◽

Injured Kidney

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Transforming growth factor-β1 in the microenvironment of ischemia reperfusion-injured kidney enhances the chemotaxis of mesenchymal stem cells to stromal cell-derived factor-1 through upregulation of surface chemokine (C-X-C motif) receptor 4

Molecular Medicine Reports ◽

10.3892/mmr.2014.1989 ◽

2014 ◽

Vol 9 (5) ◽

pp. 1794-1798 ◽

Cited By ~ 12

Author(s):

XIAO-YUN SI ◽

JING-JING LI ◽

TAO YAO ◽

XIAO-YAN WU

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Growth Factor ◽

Stromal Cell ◽

Transforming Growth Factor ◽

Ischemia Reperfusion ◽

Transforming Growth Factor Β1 ◽

Stromal Cell Derived Factor ◽

Injured Kidney

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Matching Human Unilateral AKI, a Reverse Translational Approach to Investigate Kidney Recovery after Ischemia

Journal of the American Society of Nephrology ◽

10.1681/asn.2018080808 ◽

2019 ◽

Vol 30 (6) ◽

pp. 990-1005 ◽

Cited By ~ 8

Author(s):

Danielle E. Soranno ◽

Hyo-Wook Gil ◽

Lara Kirkbride-Romeo ◽

Christopher Altmann ◽

John R. Montford ◽

...

Keyword(s):

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Renal Injury ◽

Filtration Rate ◽

Human Study ◽

Renal Ischemia ◽

Research Approach ◽

Urine Biomarkers ◽

Injured Kidney

BackgroundThe duration of renal ischemia that is associated with (or leads to) renal injury in patients is uncertain, and a reverse translational research approach has been proposed to improve animal models of AKI to facilitate clinical translatability. We developed a two murine models of unilateral renal ischemia to match a recently published human study that investigated renal injury after unilateral renal ischemia during partial nephrectomy.MethodsEight 10-week-old C57BL/6 male mice underwent left UiAKI or sham procedure, with or without intra-operative ice packs. Functional, histological, and biomarker outcomes were followed at 2, 6 and 24 hours, or 14 or 28 days later. The 14 and 28 day cohorts were duplicated such that contralateral nephrectomy could be performed 3 days prior to sacrifice with functional measurements obtained to isolate the glomerular filtration rate of the injured kidney.ResultsThe short-term outcomes correlated with the human study findings with urine and serum biomarkers of injury peaking around 24 hours and then normalizing, and reassuring immediate histological outcomes. Functional and histological outcomes at the later time-points (14 and 28 days) demonstrate an increase in fibrosis markers, and a reduction in glomerular filtration rate in the injured kidney, corresponding to the duration of ischemia, while serum and urine biomarkers remained reassuring.ConclusionsOur findings suggest that clinically available biomarkers of renal function are falsely reassuring against long-term injury following UiAKI, and that the duration of ischemia correlates with impaired function and increased fibrosis.

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RAPID RESTORATION OF INJURED KIDNEY AFTER IMMEDIATE REMOVAL OF OPPOSITE NORMAL KIDNEY In Comparison with Delayed Contralateral Nephrectomy

Pathology International ◽

10.1111/j.1440-1827.1982.tb03189.x ◽

1982 ◽

Vol 32 (5) ◽

pp. 749-757

Author(s):

Kenichi Togashi

Keyword(s):

Normal Kidney ◽

Rapid Restoration ◽

Injured Kidney

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Prevention and Management of the Critically Injured Kidney

International Anesthesiology Clinics ◽

10.1097/aia.0000000000000224 ◽

2019 ◽

Vol 57 (2) ◽

pp. 48-60 ◽

Cited By ~ 1

Author(s):

Khaled Shawwa ◽

Kianoush B. Kashani

Keyword(s):

Injured Kidney

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Expression of fibronectin splice variants in the postischemic rat kidney

AJP Renal Physiology ◽

10.1152/ajprenal.2001.280.6.f1037 ◽

2001 ◽

Vol 280 (6) ◽

pp. F1037-F1053 ◽

Cited By ~ 27

Author(s):

Anna Zuk ◽

Joseph V. Bonventre ◽

Karl S. Matlin

Keyword(s):

Extracellular Matrix ◽

Splice Variants ◽

Rat Kidney ◽

Ischemia Reperfusion ◽

Single Gene ◽

Gene Transcript ◽

Type Iii ◽

Matrix Expression ◽

Injured Kidney

Using an in vivo rat model of unilateral renal ischemia, we previously showed that the expression and distribution of fibronectin (FN), a major glycoprotein of plasma and the extracellular matrix, dramatically changes in response to ischemia-reperfusion. In the distal nephron in particular, FN accumulates in tubular lumens, where it may contribute to obstruction. In the present study, we examine whether the tubular FN is the plasma or cellular form, each of which is produced by alternative splicing of a single gene transcript. We demonstrate that FN in tubular lumens does not contain the extra type III A (EIIIA) and/or the extra type III B (EIIIB) region, both of which are unique to cellular FN. It does, however, contain the V95 region, which in the rat is a component of FNs in both plasma and the extracellular matrix. Expression of FN containing EIIIA increases dramatically in the renal interstitium after ischemic injury and continues to be produced at high levels 6 wk later. V95-containing FN also increases in the interstitial space, albeit more slowly and at lower levels than FN containing EIIIA; it also persists 6 wk later. FN containing the EIIIB region is not expressed in the injured kidney. The presence of V95 but not the EIIIA or EIIIB regions of FN in tubular lumens identifies the origin of FN in this location as the plasma; tubular FN is ultimately voided in the urine. The data indicate that both plasma and cellular FNs containing the V95 and/or EIIIA regions may contribute to the pathogenesis of acute renal failure and to the repair of the injured kidney.

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