Transforming Growth Factor-β (TGF-β) Stimulates the Expression of β1 Integrins and Adhesion by Rat Mesangial Cells

Kubo, Shoji; Kuhara, Takashi; Yasutomo, Koji; Okada, Kaname; Löster, Klemens; Reutter, Werner; Kuroda, Yasuhiro

doi:10.1006/excr.1996.0336

Cited by 67 publications

(49 citation statements)

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“…In other species, TGFB has been linked to indirect role(s) in trophoblast attachment and invasion by enhancing production of ECM proteins such as oncofetal-fibronectin (Feinberg et al 1994), inducing expression of ITGs (Zambruno et al 1995, Kagami et al 1996, Lai et al 2000, Pechkovsky et al 2008, and inhibiting trophoblast invasion by reducing production of proteases such as MMPs and plasmin (Graham & Lala 1991, Graham 1997, Kallapur et al 1999, Karmakar & Das 2002. Similar actions of TGFB may also be involved in peri-implantation events in pigs.…”

Section: Tgfb Lap and Integrins In Porcine Implantationmentioning

confidence: 99%

Transforming growth factor beta (TGFB) signaling is activated during porcine implantation: proposed role for latency-associated peptide interactions with integrins at the conceptus–maternal interface

Massuto¹,

Kneese²,

Johnson³

et al. 2010

Reproduction

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The process of implantation is mediated by a complex network of signaling and adhesive factors. In the pig, latent and active transforming growth factor beta (TGFB), TGFB receptors (TGFBR), and integrins (ITGs) are present during the peri-implantation period. TGFB signals via TGFBR and activates downstream effector SMAD proteins 2 and 3 (p-SMAD2/3). Latency-associated peptide (LAP), part of the latent TGFB complex, is known to bind to ITG heterodimers and activate TGFB. We hypothesize that active TGFBs and TGFBRs along with LAP and ITGs functionally interact at the conceptus-maternal interface to mediate events essential for conceptus development and attachment in pigs. Uteri and conceptuses from days 10, 12, 16, 20, and 24 pregnant gilts were immunostained for TGFB, LAP, and ITG subunits (ITGAV, ITGB1, ITGB3, ITGB5, ITGB6, and ITGB8). Activation of TGFBRs was evaluated by the presence of phosphorylated downstream effector SMAD2/3. Binding of LAP to ITGs was also evaluated using porcine trophectoderm cells. Abundant active TGFB was detected at the apical surfaces of epithelia at the conceptus-maternal interface, and p-SMAD2/3 was detected at both conceptus attachment and nonattachment sites during implantation. Separate aggregates of LAP, ITGB1, ITGB5, and later ITGB3 were detected at the porcine conceptus-maternal interface, and binding of LAP to ITGs on apical surfaces was demonstrated. Results suggest that functional LAP-ITG adhesion complexes support conceptus attachment and promote TGFB activation leading to TGFB interaction with TGFBR supporting events of porcine implantation.

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Section: Tgfb Lap and Integrins In Porcine Implantationmentioning

confidence: 99%

Transforming growth factor beta (TGFB) signaling is activated during porcine implantation: proposed role for latency-associated peptide interactions with integrins at the conceptus–maternal interface

Massuto¹,

Kneese²,

Johnson³

et al. 2010

Reproduction

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“…Furthermore, several growth factors, which are abundantly expressed in the tumor microenvironment, are considered potent stimulators of the integrin expression. 29,30 Recently, we have developed a DNAzyme that targeted and cleaved b1 integrin subunit mRNA in vitro and markedly reduced the adhesion and the migration of endothelial cells. It also abolished an endothelial cell capillary tube formation in fibrin and Matrigel.…”

Section: Introductionmentioning

confidence: 99%

DNAzymes to mouse β1 integrin mRNA in vivo: targeting the tumor vasculature and retarding cancer growth

et al. 2009

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Previously, we designed a DNAzyme (b1DE) targeting the human b1 integrin subunit, which efficiently digested the mRNA of the b1 integrin subunit and downregulated b1 integrin expression in endothelial cells. This DNAzyme blocked the adhesion of endothelial cells and abolished their ability to form microcapillary tubes in Matrigel. In our present study, we demonstrate that b1DE effectively inhibited neovascularization in Matrigel plugs (BALB/c mice, n ¼ 20) and solid human carcinoma tumors developed in nude mice (BALB/cA nude (nu-/-)-B6.Cg-Foxn1 nu ) (n ¼ 30) using prostate carcinoma cells PC-3 (n ¼ 15) and colon adenocarcinoma cells CX1.1 (n ¼ 15). When injected intratumorally, it significantly reduced the tumor size and number of microvessels developed by both CX1.1 and PC-3 cells within the 3 weeks of experiment duration. Thus, DNAzymes targeting b1 integrin genes can inhibit multiple key tumorigenic processes in vitro and in vivo and may serve as useful anti-cancer agents.

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“…A number of publications have identified TGF-␤1 as a critical factor in kidney diseases such as glomerulosclerosis (21) and mesangioproliferative glomerulonephritis (22). Furthermore, it has been shown that TGF-␤1 augments the accumulation of glomerular matrix through its induction of collagen type I (23).…”

mentioning

confidence: 99%

SPARC Regulates the Expression of Collagen Type I and Transforming Growth Factor-β1 in Mesangial Cells

Francki¹,

Bradshaw²,

Bassuk³

et al. 1999

Journal of Biological Chemistry

173

140

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The matricellular protein SPARC is expressed at high levels in cells that participate in tissue remodeling and is thought to regulate mesangial cell proliferation and extracellular matrix production in the kidney glomerulus in a rat model of glomerulonephritis (Pichler, R. H., Bassuk, J. A., Hugo, C., Reed, M. J., Eng, E., Gordon, K. L., Pippin, J., Alpers, C. E., Couser, W. G., Sage, E. H., and Johnson, R. J. (1997) Am. J. Pathol. 148, 1153-1167). A potential mechanism by which SPARC controls both cell cycle and matrix production has been attributed to its regulation of a pleiotropic growth factor. In this study we used primary mesangial cell cultures from wild-type mice and from mice with a targeted disruption of the SPARC gene. SPARC-null cells displayed diminished expression of collagen type I mRNA and protein, relative to wild-type cells, by the criteria of immunocytochemistry, immunoblotting, and the reverse transcription-polymerase chain reaction. The SPARC-null cells also showed significantly decreased steady-state levels of transforming growth factor-␤1 (TGF-␤1) mRNA and secreted TGF-␤1 protein. Addition of recombinant SPARC to SPARC-null cells restored the expression of collagen type I mRNA to 70% and TGF-␤1 mRNA to 100% of wildtype levels. We conclude that SPARC regulates the expression of collagen type I and TGF-␤1 in kidney mesangial cells. Since increased mitosis and matrix deposition by mesangial cells are characteristics of glomerulopathies, we propose that SPARC is one of the factors that maintains the balance between cell proliferation and matrix production in the glomerulus.

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Transforming Growth Factor-β (TGF-β) Stimulates the Expression of β1 Integrins and Adhesion by Rat Mesangial Cells

Cited by 67 publications

References 0 publications

Transforming growth factor beta (TGFB) signaling is activated during porcine implantation: proposed role for latency-associated peptide interactions with integrins at the conceptus–maternal interface

Transforming growth factor beta (TGFB) signaling is activated during porcine implantation: proposed role for latency-associated peptide interactions with integrins at the conceptus–maternal interface

DNAzymes to mouse β1 integrin mRNA in vivo: targeting the tumor vasculature and retarding cancer growth

SPARC Regulates the Expression of Collagen Type I and Transforming Growth Factor-β1 in Mesangial Cells

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