Intrarenal Injection of Bone Marrow-Derived Angiogenic Cells Reduces Endothelial Injury and Mesangial Cell Activation in Experimental Glomerulonephritis

Uchimura, Hidemasa; Marumo, Takeshi; Takase, Osamu; Kawachi, Hiroshi; Shimizu, Fujio; Hayashi, Matsuhiko; Saruta, Takao; Hishikawa, Keiichi; Fujita, Toshiro

doi:10.1681/asn.2004050367

Cited by 92 publications

(72 citation statements)

References 30 publications

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“…In addition, intrarenal injection of culture modified bone marrow-derived angiogenic cells reduced endothelial injury in experimental glomerulonephritis. 43 Thus, the vasculogenic potential of bone marrow-derived cells, previously shown in heart infarct or retinal neovascularization, 44,45 can be demonstrated in injured kidneys.…”

Section: Discussionmentioning

confidence: 91%

Organ-injury-induced reactivation of hemangioblastic precursor cells

et al. 2007

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Early in mammalian development, the stem cell leukemia (SCL/TAL1) gene and its distinct 3 0 enhancer (SCL 3 0 En) specify bipotential progenitor cells that give rise to blood and endothelium, thus termed hemangioblasts. We have previously detected a minor population of SCL ( þ ) cells in the postnatal kidney. Here, we demonstrate that cells expressing the SCL 3 0 En in the adult kidney are comprised of CD45 þ CD31À hematopoietic cells, CD45ÀCD31 þ endothelial cells and CD45ÀCD31À interstitial cells. Creation of bone marrow chimeras of SCL 3 0 En transgenic mice into wild-type hosts shows that all three types of SCL 3 0 En-expressing cells in the adult kidney can originate from the bone marrow. Ischemia/ reperfusion injury to the adult kidney of SCL 3 0 En transgenic mice results in the intrarenal elevation of SCL and FLK1 mRNA levels and of cells expressing hem-endothelial progenitor markers (CD45, CD34, c-Kit and FLK1). Furthermore, analysis of SCL 3 0 En in the ischemic kidneys reveals an increase in the abundance of SCL 3 0 En-expressing cells, predominantly within the CD45 ( þ ) hematopoietic fraction and to a lesser extent in the CD45 (À) fraction. Our results suggest organ-injury-induced reactivation of bone marrow-derived hemangioblasts and possible local angioblastic progenitors expressing SCL and SCL 3 0 En.

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Section: Discussionmentioning

confidence: 91%

Organ-injury-induced reactivation of hemangioblastic precursor cells

et al. 2007

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“…We showed previously that BMPCs obtained using this method differentiated into endothelial cells after injection and exerted angiogenic effects on the glomerular capillaries in nephritic rats. 20 To evaluate the effects of aldosterone on BMPC formation, bone marrow mononuclear cells were incubated for 4 days in the presence or absence of the hormone (10 to 1000 nmol/L). Thereafter, BMPCs were trypsinized and counted using a hemocytometer.…”

Section: Bmpc Culturementioning

confidence: 99%

“…Because BMPCs produce a significant amount of VEGF, 20 aldosterone may inhibit the formation of BMPCs by reducing VEGF production. Production ( Figure 3A) and mRNA levels ( Figure 3B) of VEGF were, however, not significantly altered by aldosterone (PϾ 0.05).…”

Section: Effects Of Aldosterone On the Expression Of Angiogenic Factomentioning

confidence: 99%

Aldosterone Impairs Bone Marrow–Derived Progenitor Cell Formation

et al. 2006

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Abstract-Aldosterone has been suggested recently to cause vascular injury by directly acting on the vasculature, in addition to causing injury by raising the blood pressure. Bone marrow-derived endothelial progenitor cells (EPCs) have been shown to exert an important role in the repair of the endothelium. In addition, cell-based therapy using EPCs is emerging as a novel therapeutic strategy for myocardial and peripheral vascular diseases. However, impaired formation and function of EPCs has been observed in patients with risk factors for cardiovascular diseases. We evaluated the possible effects of aldosterone on EPCs by examining the progenitor cell formation from bone marrow mononuclear cells ex vivo. Aldosterone (10 to 1000 nmol/L) reduced the formation of progenitor cells in a concentration-dependent manner. This effect of aldosterone was attenuated by cotreatment with spironolactone. Aldosterone reduced the mRNA levels of vascular endothelial growth factor (VEGF) receptor (VEGFR) 2 without having any effect on the production of VEGF or mRNA levels of VEGF and hepatocyte growth factor in the progenitor cells. However, the expression of stromal-derived growth factor 1 mRNA was paradoxically increased. Consistent with the downregulation of VEGFR-2, VEGF-induced phosphorylation of Akt was abolished in the progenitor cells after aldosterone treatment. N-acetylcysteine, an antioxidant, attenuated the inhibitory effects of aldosterone. These data indicate that aldosterone inhibits the formation of bone marrow-derived progenitor cells, at least partly, by attenuating VEGFR-2 expression and the subsequent Akt signaling.

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“…MSCs can express several growth factors such as hepatocyte growth factor, VEGF and insulin like growth factor-1, all known to improve renal function, mediated by their antiapoptotic, mitogenic and other cytokine actions. These paracrine actions of MSCs result in the renal down regulation of proinflammatory cytokines IL-1-β, TNF-α, and IFN-γ, as well as inducible nitric oxide synthase and up regulation of anti-inflammatory and organ-protective interleukin-10, as well as basic fibroblast growth factor, TGF-α and antiapoptotic Bc1-2 [41] .…”

Section: Discussionmentioning

confidence: 99%