Thrombospondin binds and activates the small and large forms of latent transforming growth factor-beta in a chemically defined system.

Schultz‐Cherry, Stacey; Ribeiro, Solange M. F.; Gentry, L E; Murphy-Ullrich, Joanne E.

doi:10.1016/s0021-9258(18)47086-x

Cited by 250 publications

(28 citation statements)

References 42 publications

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“…The mechanism of activation of latent TGF-␤ is not well understood. Before TGF-␤ is activated by plasmin, thrombospondin [41] or other mechanisms to release mature TGF-␤, ECM-bound LLTC has to be released by the proteases from ECM. Hence, the LLTC-ECM interaction via LTBP-1 may be the first step in the sequence of activation process for TGF-␤ [21,22,42].…”

Section: Discussionmentioning

confidence: 99%

Anti-latent TGF-β binding protein-1 antibody or synthetic oligopeptides inhibit extracellular matrix expression induced by stretch in cultured rat mesangial cells

Hori¹,

Katoh²,

Hirakata³

et al. 1998

Kidney International

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Transforming growth factor-beta (TGF-beta) is usually secreted as a large latent complex associated with latent TGF-beta binding protein-1 (LTBP-1), which is known to bind to extracellular matrix (ECM) components. Although the LTBP-ECM interaction has been suggested to play a role in the activation and biological action of TGF-beta, the precise mechanism is still unclear. In glomerular hypertension mesangial cells are believed to perceive the increased cyclic strain and we have recently reported that cyclic mechanical stretch in vitro enhances the expression of ECM components via an autocrine/paracrine secretion of TGF-beta in cultured rat mesangial cells. Therefore, in this study we examined the role of LTBP-1 in the stretch-induced, TGF-beta-mediated ECM expression. Mesangial cells expressed mRNA for short and long forms of LTBP-1 (LTBP-1S and LTBP-1L, respectively). Mesangial cells were subjected to cyclic stretch to provide a maximal elongation of 20% at a rate of 60 cycles/min for 24 to 36 hours in the presence of polyclonal antibody raised against human LTBP-1 or synthetic oligopeptides corresponding to the N-terminal portions of human LTBP-1, which may work as competitive inhibitors against the LTBP-ECM association. Both anti-LTBP-1 antibody (Ab39) and synthetic oligopeptides inhibited the stretch-induced mRNA expression of type I collagen and fibronectin in a dose-dependent manner, but the inhibition by Ab39 or the oligopeptides was recovered by adding recombinant TGF-beta. Ab39 or the oligopeptides did not change the effect of exogenously added TGF-beta, such as growth-inhibition in mink lung epithelial cells. These results suggest that mesangial cells secrete TGF-beta as a large latent complex, and the LTBP-ECM interaction may be a pivotal step in TGF-beta action and ECM accumulation, providing a new therapeutic strategy against progression of glomerulosclerosis and other fibrotic diseases.

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Section: Discussionmentioning

confidence: 99%

Anti-latent TGF-β binding protein-1 antibody or synthetic oligopeptides inhibit extracellular matrix expression induced by stretch in cultured rat mesangial cells

Hori¹,

Katoh²,

Hirakata³

et al. 1998

Kidney International

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“…TSP-1 is also a major activator of latent TGF β [ 99 , 100 ]. TGF β in complex with TSP-1 is biologically active and favors TGF β binding to cell receptors [ 101 ]. Platelets, endothelial cells, smooth muscle cells, neutrophils, monocytes, macrophages, alveolar macrophages, fibroblasts, and epithelial cells all produce TSP-1 [ 102 – 106 ].…”

Section: Mechanisms Of Pfmentioning

confidence: 99%

Idiopathic Pulmonary Comorbidities and Mechanisms

Pacurari

Mitra

Turner

2021

International Journal of Inflammation

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Idiopathic pulmonary fibrosis (IPF) is a disease with an unknown etiology mainly characterized by a progressive decline of lung function due to the scarring of the tissue deep in the lungs. The overall survival after diagnosis remains low between 3 and 5 years. IPF is a heterogeneous disease and much progress has been made in the past decade in understanding the disease mechanisms that contributed to the development of two new drugs, pirfenidone and nintedanib, which improved the therapeutic management of the disease. The understanding of the cofactors and comorbidities of IPF also contributed to improved management of the disease outcome. In the present review, we evaluate scientific evidence which indicates IPF as a risk factor for other diseases based on the complexity of molecular and cellular mechanisms involved in the disease development and of comorbidities. We conclude from the existing literature that while much progress has been made in understating the mechanisms involved in IPF development, further studies are still necessary to fully understand IPF pathogenesis which will contribute to the identification of novel therapeutic targets for IPF management as well as other diseases for which IPF is a major risk factor.

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“…TSP1 is one of the most characterized physiologic activators of TGFβ1 in vitro and in vivo (Schultz-Cherry et al 1994). We have previously demonstrated that an in vivo treatment with TSP1 analogues improve pituitary levels of active TGFβ1, decreasing hyperprolactinemia in female rats carrying prolactinomas (Recouvreux et al 2012).…”

Section: Journal Of Endocrinologymentioning

confidence: 99%

TGFβ1 regulates prolactin secretion during postnatal development: gender differences

Abeledo-Machado

Pérez

Camilletti

et al. 2020

Journal of Endocrinology

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Serum prolactin levels gradually increase from birth to puberty in both male and female rats, with higher levels observed in female since the first days of life. The increase in lactotroph secretion was attributed to the maturation of prolactin-inhibiting and prolactin-releasing factors; however, those mechanisms could not fully explain the gender differences observed. Prolactin secretion from isolated lactotrophs, in the absence of hypothalamic control, also increases during the first weeks of life, suggesting the involvement of intra-pituitary factors. We postulate that pituitary transforming growth factor beta 1 (TGFβ1) is involved in the regulation of prolactin secretion as well as in the gender differences observed at early postnatal age. Several components of the local TGFβ1 system were evaluated during postnatal development (11, 23, and 45 days) in female and male Sprague–Dawley rats. In vivo assays were performed to study local TGFβ1 activation and its impact on prolactin secretion. At day 11, female pituitaries present high levels of active TGFβ1, concomitant with the highest expression of TGFβ1 target genes and the phospho-Smad3 immunostaining in lactotrophs. The steady increase in prolactin secretion inversely correlates with active TGFβ1 levels only in females. Dopamine and estradiol induce TGFβ1 activation at day 11, in both genders, but its activation induces the inhibition of prolactin secretion only in females. Our findings demonstrate that: (1) TGFβ1 activation is regulated by dopamine and estradiol; (2) the inhibitory regulation of local TGFβ1 on prolactin secretion is gender specific; and (3) this mechanism is responsible, at least partially, for the gender differences observed being relevant during postnatal development.

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Thrombospondin binds and activates the small and large forms of latent transforming growth factor-beta in a chemically defined system.

Cited by 250 publications

References 42 publications

Anti-latent TGF-β binding protein-1 antibody or synthetic oligopeptides inhibit extracellular matrix expression induced by stretch in cultured rat mesangial cells

Anti-latent TGF-β binding protein-1 antibody or synthetic oligopeptides inhibit extracellular matrix expression induced by stretch in cultured rat mesangial cells

Idiopathic Pulmonary Comorbidities and Mechanisms

TGFβ1 regulates prolactin secretion during postnatal development: gender differences

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