Infiltration of Nestin-Expressing Cells in Interstitial Fibrosis in Chronic Cyclosporine Nephropathy

Ahn, Kyung Ohk; Li, Can; Lim, Sun Woo; Song, Ho Kyung; Ghee, Jung Yeon; Kim, Su Hyun; Kim, Jin Young; Yoon, Hye Eun; Ho, Jung; Kim, Jin; Yang, Chul Woo

doi:10.1097/tp.0b013e3181820470

Cited by 9 publications

(11 citation statements)

References 26 publications

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“…In contrast to experimental renal damage by chronic application of cyclosporin, where no quantitative changes in nestin mRNA were measured , we observed changes in nestin mRNA and protein expression. The immunoreactivity detected in immunoblots essentially correlated with changes in nestin mRNA, suggesting that nestin expression is at least partially regulated at the level of mRNA synthesis or stability.…”

Section: Discussioncontrasting

confidence: 96%

Expression of nestin after renal transplantation in the rat

Skwirba

Zakrzewicz

Atanasova

et al. 2014

APMIS

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Chronic allograft injury (CAI) limits the long-term success of renal transplantation. Nestin is a marker of progenitor cells, which probably contribute to its pathogenesis. We hypothesize that nestin is induced by ischemia/reperfusion injury and acute rejection, main risk factors for CAI. Syngeneic renal transplantation was performed in Lewis rats and allogeneic transplantation in the Fischer 344 to Lewis strain combination, which results in reversible acute rejection and in CAI in the long-run. The Dark Agouti to Lewis rat strain combination was used to study fatal acute rejection. In untreated kidneys, nestin immunoreactivity was detected in glomeruli and in very few interstitial or microvascular cells. Syngeneic transplantation induced nestin expression within 4 days, which decreased until day 9 and returned to control levels on day 42. Nestin expression was strong during acute rejection and still detected during the pathogenesis of CAI on day 42. Nestin-positive cells were identified as endothelial cells and interstitial fibroblast-like cells co-expressing alpha-smooth muscle actin. A sub-population of them expressed proliferating cell nuclear antigen. In conclusion, nestin is induced in renal grafts by ischemia/reperfusion injury and acute rejection. It is expressed by proliferating myofibroblasts and endothelial cells and probably contributes to the pathogenesis of CAI.

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Section: Discussioncontrasting

confidence: 96%

Expression of nestin after renal transplantation in the rat

Skwirba

Zakrzewicz

Atanasova

et al. 2014

APMIS

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“…However, Iwano and coworkers [44] have demonstrated that myofibroblasts could originate from bone marrow in a mouse model of UUO, raising the risk of enhancing fibrosis, even though these myfibroblasts were non-functional [47,48]. In a model of chronic ciclosporine nephropathy, Ahn and coworkers [48] showed an increase in nestin expressing cells in renal interstitium which correlates with increased fibrosis. We found, however, that BMMC ameliorated rather than worsened tissue fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Bone Marrow Mononuclear Cells Attenuate Interstitial Fibrosis and Stimulate the Repair of Tubular Epithelial Cells after Unilateral Ureteral Obstruction

Barreira

Takiya²,

Castiglione

et al. 2009

Cell Physiol Biochem

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The growing number of patients suffering from chronic renal disease is a challenge for the development of innovative therapies. Benefits of cell therapy in acute renal diseases in animal models have been reported but seldom for chronic lesions. We present evidence for the improvement of renal morphology in a model of tubulointerstitial fibrosis. Wistar rats were submitted to unilateral ureteral obstruction (UUO), treated with bone-marrow mononuclear cells (UUO+BMMC) infused via the cava vein, and killed on day 14. Labeled BMMC were seen in renal tissue after 7 days in the group UUO+BMMC. UUO+BMMC also showed a reduction in ED1⁺ cells and tubular apoptotic cells together with enhanced tubular proliferation. Myofibroblasts were also reduced after BMMC which is consistent with a decrease in collagen deposition (picro Sirius staining) and RT-PCR data showing lower levels of procollagen-I mRNA. Simultaneously, nestin+ cells increased in the interstitium and decreased in the tubules. Double stained nestin⁺/α-SMA⁺ cells were present only in the interstitium, and their levels did not change after BMMC infusion. These data indicate a renoprotective effect of BMMC through increased tubular cell regeneration, inhibition of tubular cell apoptosis and partially blocking of the inflammatory and fibrotic events that occur after unilateral ureteral obstruction.

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“…It is possible that CsA-induced renal injury upregulates several molecules whose presence causes retention of systemically infused MSCs. One study showed recruitment of nestin-expressing cells to areas of CsA-induced renal injury where they play a role in the repair of injured tissues and organs [24].…”

Section: Discussionmentioning

confidence: 99%

Human Adipose Tissue Derived Mesenchymal Stem Cells Aggravate Chronic Cyclosporin Nephrotoxicity by the Induction of Oxidative Stress

et al. 2013

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The aim of this study was to investigate whether hATMSCs protect against cyclosporine (CsA)-induced renal injury. CsA (7.5 mg/kg) and hATMSCs (3×106/5 mL) were administered alone and together to rats for 4 weeks. The effect of hATMSCs on CsA-induced renal injury was evaluated by assessing renal function, interstitial fibrosis, infiltration of inflammatory cells, and apoptotic cell death. Four weeks of CsA-treatment produced typical chronic CsA-nephropathy. Combined treatment with CsA and hATMSCs did not prevent these effects and showed a trend toward further renal deterioration. To evaluate why hATMSCs aggravated CsA-induced renal injury, we measured oxidative stress, a major mechanism of CsA-induced renal injury. Both urine and serum 8-hydroxydeoxyguanosine(8-OHdG) levels were higher in the CsA+hATMSCs group than in the CsA group (P<0.05). An in vitro study showed similar results. Although the rate of apoptosis did not differ significantly between HK-2 cells cultured in hATMSCs-conditioned medium and those cultured in DMEM, addition of CsA resulted in greater apoptosis in HK-2 cells cultured in hATMSCs-conditioned medium. Addition of CsA increased oxidative stress in the hATMSCs-conditioned medium. The results of our study suggest that treatment with hATMSCs may aggravate CsA-induced renal injury because hATMSCs cause oxidative stress in the presence of CsA.

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Infiltration of Nestin-Expressing Cells in Interstitial Fibrosis in Chronic Cyclosporine Nephropathy

Abstract: CsA-induced renal injury recruits nestin-expressing cells to injured areas, and these cells might be involved in reparative fibrosis in the progression of chronic CsA nephropathy.

Cited by 9 publications

References 26 publications

Expression of nestin after renal transplantation in the rat

Expression of nestin after renal transplantation in the rat

Bone Marrow Mononuclear Cells Attenuate Interstitial Fibrosis and Stimulate the Repair of Tubular Epithelial Cells after Unilateral Ureteral Obstruction

Human Adipose Tissue Derived Mesenchymal Stem Cells Aggravate Chronic Cyclosporin Nephrotoxicity by the Induction of Oxidative Stress

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