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VEGF is a mediator of the renoprotective effects of multipotent marrow stromal cells in acute kidney injury.

Tögel F, Zhang P, Hu Z, Westenfelder C - J. Cell. Mol. Med. (2008)

Bottom Line: Knockdown of vascular enthothelial growth factor (VEGF) by siRNA reduced effectiveness of MSCs in the treatment of ischemic AKI in a rat model.Animals treated with MSCs had increased renal microvessel density compared to VEGF knockdown MSC-treated and vehicle-treated animals.These results show that VEGF is an important mediator of the early and late phase of renoprotective action after AKI in the context of stem cell treatment.

View Article: PubMed Central - PubMed

Affiliation: University of Utah, Division of Nephrology, Department of Medicine, Salt Lake City, UT 84148, USA.

ABSTRACT
Adult stem cell treatment of complex disorders is a promising therapeutic approach and multipotent marrow stromal cells (MSCs) have been shown to be effective in various animal models of diseases. Acute kidney injury (AKI) is a common and serious problem in hospitalized patients and bone marrow derived multipotent MSCs have been shown to be effective in different models of AKI. The mechanism of action of MSCs is complex but involves paracrine actions including growth factor secretion. Knockdown of vascular enthothelial growth factor (VEGF) by siRNA reduced effectiveness of MSCs in the treatment of ischemic AKI in a rat model. Animals treated with MSCs had increased renal microvessel density compared to VEGF knockdown MSC-treated and vehicle-treated animals. These results show that VEGF is an important mediator of the early and late phase of renoprotective action after AKI in the context of stem cell treatment.

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Related in: MedlinePlus

In vitro study to determine the effect of VEGF knockdown on proliferation of MSC‐conditioned medium (MSC CM) on NRK cells using the MTT assay. Data are shown as mean + S.D. (n= 6 per group). S.F. = serum free medium. (−) siRNA = negative control (irrelevant) siRNA. MSC CM after knockdown of VEGF significantly reduced proliferation of NRK cells compared to negative control siRNA (P= 0.029), and control MSC CM (P= 0.038). Addition of 10 ng/ml VEGF (S.F. + VEGF) brought proliferation back to baseline. 10% FBS as positive control showed the highest proliferative activity.
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f2: In vitro study to determine the effect of VEGF knockdown on proliferation of MSC‐conditioned medium (MSC CM) on NRK cells using the MTT assay. Data are shown as mean + S.D. (n= 6 per group). S.F. = serum free medium. (−) siRNA = negative control (irrelevant) siRNA. MSC CM after knockdown of VEGF significantly reduced proliferation of NRK cells compared to negative control siRNA (P= 0.029), and control MSC CM (P= 0.038). Addition of 10 ng/ml VEGF (S.F. + VEGF) brought proliferation back to baseline. 10% FBS as positive control showed the highest proliferative activity.

Mentions: NRK cells express VEGF receptors Flt‐1, flt‐4 and flk‐1 as determined by PCR and showed proliferative activity when VEGF was added to the medium (data not shown). VEGF knockdown with siRNA reduced VEGF protein levels in MSC conditioned medium (Fig. 1, right panel). Conditioned medium from VEGF knockdown MSC exerted less proliferative activity on proximal tubular cells compared to regular conditioned medium from MSCs treated with irrelevant siRNAs (P= 0.029) or control medium (S.F. [serum‐free medium], P= 0.038) (Fig. 2), thereby demonstrating the mitogenic activity of VEGF in tubular cells. Addition of 10 ng/ml VEGF restored proliferative activity of the conditioned medium.


VEGF is a mediator of the renoprotective effects of multipotent marrow stromal cells in acute kidney injury.

Tögel F, Zhang P, Hu Z, Westenfelder C - J. Cell. Mol. Med. (2008)

In vitro study to determine the effect of VEGF knockdown on proliferation of MSC‐conditioned medium (MSC CM) on NRK cells using the MTT assay. Data are shown as mean + S.D. (n= 6 per group). S.F. = serum free medium. (−) siRNA = negative control (irrelevant) siRNA. MSC CM after knockdown of VEGF significantly reduced proliferation of NRK cells compared to negative control siRNA (P= 0.029), and control MSC CM (P= 0.038). Addition of 10 ng/ml VEGF (S.F. + VEGF) brought proliferation back to baseline. 10% FBS as positive control showed the highest proliferative activity.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4940776&req=5

f2: In vitro study to determine the effect of VEGF knockdown on proliferation of MSC‐conditioned medium (MSC CM) on NRK cells using the MTT assay. Data are shown as mean + S.D. (n= 6 per group). S.F. = serum free medium. (−) siRNA = negative control (irrelevant) siRNA. MSC CM after knockdown of VEGF significantly reduced proliferation of NRK cells compared to negative control siRNA (P= 0.029), and control MSC CM (P= 0.038). Addition of 10 ng/ml VEGF (S.F. + VEGF) brought proliferation back to baseline. 10% FBS as positive control showed the highest proliferative activity.
Mentions: NRK cells express VEGF receptors Flt‐1, flt‐4 and flk‐1 as determined by PCR and showed proliferative activity when VEGF was added to the medium (data not shown). VEGF knockdown with siRNA reduced VEGF protein levels in MSC conditioned medium (Fig. 1, right panel). Conditioned medium from VEGF knockdown MSC exerted less proliferative activity on proximal tubular cells compared to regular conditioned medium from MSCs treated with irrelevant siRNAs (P= 0.029) or control medium (S.F. [serum‐free medium], P= 0.038) (Fig. 2), thereby demonstrating the mitogenic activity of VEGF in tubular cells. Addition of 10 ng/ml VEGF restored proliferative activity of the conditioned medium.

Bottom Line: Knockdown of vascular enthothelial growth factor (VEGF) by siRNA reduced effectiveness of MSCs in the treatment of ischemic AKI in a rat model.Animals treated with MSCs had increased renal microvessel density compared to VEGF knockdown MSC-treated and vehicle-treated animals.These results show that VEGF is an important mediator of the early and late phase of renoprotective action after AKI in the context of stem cell treatment.

View Article: PubMed Central - PubMed

Affiliation: University of Utah, Division of Nephrology, Department of Medicine, Salt Lake City, UT 84148, USA.

ABSTRACT
Adult stem cell treatment of complex disorders is a promising therapeutic approach and multipotent marrow stromal cells (MSCs) have been shown to be effective in various animal models of diseases. Acute kidney injury (AKI) is a common and serious problem in hospitalized patients and bone marrow derived multipotent MSCs have been shown to be effective in different models of AKI. The mechanism of action of MSCs is complex but involves paracrine actions including growth factor secretion. Knockdown of vascular enthothelial growth factor (VEGF) by siRNA reduced effectiveness of MSCs in the treatment of ischemic AKI in a rat model. Animals treated with MSCs had increased renal microvessel density compared to VEGF knockdown MSC-treated and vehicle-treated animals. These results show that VEGF is an important mediator of the early and late phase of renoprotective action after AKI in the context of stem cell treatment.

Show MeSH
Related in: MedlinePlus