Expression of bone morphogenetic protein-7 mRNA in normal and ischemic adult rat kidney

Simon, Matthias; Maresh, J. Gregory; Harris, S. E.; Hernandez, James D.; Arar, Mazen Y; Olson, Merle S.; Abboud, Hanna E.

doi:10.1152/ajprenal.1999.276.3.f382

Cited by 90 publications

(102 citation statements)

References 32 publications

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“…[35][36][37][38][39][40] This raises the question of whether there is normally ongoing expression of BMP7 in the adult kidney and, if so, what its source is. The podocyte expression of BMP7, as judged by in situ hybridization, seems to diminish in the most mature glomeruli; however it is possible that expression of BMP7 in podocytes continues at a low level throughout adulthood.…”

Section: Discussionmentioning

confidence: 99%

Podocyte-Derived BMP7 Is Critical for Nephron Development

Kazama

Mahoney

Miner

et al. 2008

Journal of the American Society of Nephrology

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Individuals with congenital renal hypoplasia display a defect in the growth of nephrons during development. Many genes that affect the initial induction of nephrons have been identified, but little is known about the regulation of postinductive stages of kidney development. In the absence of the growth factor bone morphogenic protein 7 (BMP7), kidney development arrests after induction of a small number of nephrons. The role of BMP7 after induction, however, has not been fully investigated. Here, we generated a podocyte-specific conditional knockout of BMP7 (Bmp7 flox/flox ;Nphs2-Cre ϩ [BMP7 CKO]) to study the role of podocyte-derived BMP7 in nephron maturation. By postnatal day 4, 65% of BMP7 CKO mice had hypoplastic kidneys, but glomeruli demonstrated normal patterns of laminin and collagen IV subunit expression. Developing proximal tubules, however, were reduced in number and demonstrated impaired cellular proliferation. We examined signaling pathways downstream of BMP7; the level of cortical phosphorylated Smad1, 5, and 8 was unchanged in BMP CKO kidneys, but phosphorylated p38 mitogen-activated protein kinase was significantly decreased. In addition, ␤-catenin was reduced in BMP7 CKO kidneys, and its localization to intracellular vesicles suggested that it had been targeted for degradation. In summary, these results define a BMP7-mediated regulatory axis between glomeruli and proximal tubules during kidney development.

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Section: Discussionmentioning

confidence: 99%

Podocyte-Derived BMP7 Is Critical for Nephron Development

Kazama

Mahoney

Miner

et al. 2008

Journal of the American Society of Nephrology

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“…It plays major roles during renal and eye development (8). In adults, BMP7 expression is very limited, and tissues with greatest levels include the kidney (7,22). Its function in the kidney is largely unknown.…”

Section: Discussionmentioning

confidence: 99%

“…BMP7 plays major roles during embryonic development, but in adult organisms expression of BMP7 and its receptors is retained in only few tissues, most prominently in the kidney (3,4,22,29). Its functions in adult kidney are presently unknown but may include promotion of differentiated epithelial phenotype in tubular cells (7,8,31).…”

mentioning

confidence: 99%

BMP7 antagonizes TGF-β-dependent fibrogenesis in mesangial cells

Wang

Hirschberg

2003

American Journal of Physiology-Renal Physiology

176

142

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Exogenous administration of recombinant human bone morphogenetic protein (BMP)-7 was recently shown to ameliorate renal glomerular and interstitial fibrosis in rodents with experimental renal diseases. We tested the hypothesis that BMP7 functions by antagonizing profibrogenic events that are induced by transforming growth factor (TGF)-β in cultured mesangial cells. Incubation of murine mesangial cells with TGF-β (50–200 pM) increased cell-associated collagen type IV and fibronectin, soluble collagen type IV, thrombospondin, and connective tissue growth factor (CTGF). Coincubation with recombinant human BMP7 (200 pM) reduced the increase of these ECM proteins and CTGF. The changes in collagen type IV and fibronectin proteins occurred without concomitant changes in collagen type α1IV and fibronectin mRNA levels, suggesting that TGF-β and BMP7 act primarily by affecting ECM protein degradation. Indeed, TGF-β decreases the levels and activity of matrix metalloprotease (MMP)-2, the major metalloprotease that is secreted by mesangial cells. Moreover, BMP7 inhibits TGF-β-induced activation of MMP2. Because TGF-β reduces the activity of MMPs through increasing plasminogen activator inhibitor (PAI)-1, we tested whether BMP7 interferes with this TGF-β effect. BMP7 reduces, by about two-thirds, the activation of a PAI-1 promoter/luciferase reporter in cells stably transfected with this construct. The findings from these studies indicate that BMP7 reduces TGF-β-induced ECM protein accumulation in cultured mesangial cells primarily by maintaining levels and activity of MMP2 partially through prevention of TGF-β-dependent upregulation of PAI-1.

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“…Administration of recombinant BMP7 during acute renal failure in rats preserved renal epithelial cell morphology and improved renal function. BMP-7 also enhanced recovery when infused into rats with ischemia-induced acute renal failure [62]. In rat metanephric mesenchymal cells, inhibition of BMP7 signalling using antisense oligonucleotides or anti-BMP-7 antibodies blocked epithelial differentiation in a subpopulation of cells.…”

Section: Bmps Emt and Fibrotic Diseasementioning

confidence: 98%