Mitogenic activity of endothelin on human cultured prostatic smooth muscle cells

Saita, Yuji; Yazawa, Hidenori; Koizumi, Tomonobu; Morita, Takashi; Tamura, Toshinari; Takenaka, Toichi; Honda, Kazuo

doi:10.1016/s0014-2999(98)00183-6

Cited by 30 publications

(25 citation statements)

References 27 publications

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“…For example, ET, SP, ATP and angiotensin II have all been shown to produce growth and\or proliferation of smooth muscle cells (see Schachter, 1990 ;Erlinge, 1998 ;Saita et al 1998). This is of particular interest for pathological conditions such as hypertension, atherosclerosis, restenosis following angioplasty, diabetes .…”

Section: Long-term Trophic Actions Of Substances Released From Endothmentioning

confidence: 99%

Release of vasoactive substances from endothelial cells by shear stress and purinergic mechanosensory transduction

1999

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The evidence for release of vasoactive substances from endothelial cells in response to shear stress caused by the viscous drag of passing fluids is reviewed and, in particular, its physiological significance both in shortterm regulation of blood vessel tone and in long-term regulation of cell growth, differentiation, proliferation, and cell death in pathophysiological conditions is discussed. A new concept of purinergic mechanosensory transduction, particularly in relation to nociception, is introduced. It is proposed that distension of tubes (including ureter, vagina, salivary and bile ducts, gut) and sacs (including urinary and gall bladders, and lung) leads to release of ATP from the lining epithelium, which then acts on P2X #/$ receptors on subepithelial sensory nerves to convey information to the CNS.

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Section: Long-term Trophic Actions Of Substances Released From Endothmentioning

confidence: 99%

Release of vasoactive substances from endothelial cells by shear stress and purinergic mechanosensory transduction

1999

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“…ET-1 demonstrates a wide range of biological properties on normal cells (Rubanyi and Botelho, 1991;Levin, 1995), including significant mitogenic activity toward a number of cell types, such as smooth muscle cells and fibroblasts, and the modification of extracellular matrix metabolism (Levin, 1995;Saita et al, 1998;Xu et al, 1998;Shi-Wen et al, 2001). In addition, ET-1 has been reported to promote the contractile ability of normal dermal fibroblasts (Guidry and Hook, 1991;Appleton et al, 1992), which is essential for wound closure and reconstitution of the dermis (Grinnell, 1994), but also contributes to scar formation (Schmitt-Graff et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

“…The enzyme responsible for the specific cleavage at Trp-21 has been termed endothelin-converting enzyme; it is a neutral membranebound metalloproteinase with M r ϭ 120 kDa, belonging to the endo-peptidase-24.11 family found in brain (Ohnaka et al, 1993;Turner and Murphy, 1996). Injury and the wound healing response lead to stabilization of endothelin-converting enzyme-1 mRNA and to the generation of bioactive endothelin (Shao et al, 2003).ET-1 demonstrates a wide range of biological properties on normal cells (Rubanyi and Botelho, 1991;Levin, 1995), including significant mitogenic activity toward a number of cell types, such as smooth muscle cells and fibroblasts, and the modification of extracellular matrix metabolism (Levin, 1995;Saita et al, 1998;Xu et al, 1998;Shi-Wen et al, 2001). In addition, ET-1 has been reported to promote the contractile ability of normal dermal fibroblasts (Guidry and Hook, 1991;Appleton et al, 1992), which is essential for wound closure and reconstitution of the dermis (Grinnell, 1994), but also contributes to scar formation (Schmitt-Graff et al, 1994).…”

mentioning

confidence: 99%

Endothelin-1 Promotes Myofibroblast Induction through the ETA Receptor via a rac/Phosphoinositide 3-Kinase/Akt-dependent Pathway and Is Essential for the Enhanced Contractile Phenotype of Fibrotic Fibroblasts

Chen

Denton

et al. 2004

MBoC

326

307

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The endothelins are a family of endothelium-derived peptides that possess a variety of functions, including vasoconstriction. Endothelin-1 (ET-1) is up-regulated during tissue repair and promotes myofibroblast contraction and migration, hence contributing to matrix remodeling during tissue repair. Here, we show that addition of ET-1 to normal lung fibroblasts induces expression of proteins that contribute to a contractile phenotype, including ␣-smooth muscle actin (␣-SMA), ezrin, moesin, and paxillin. We confirm that ET-1 enhances the ability of lung fibroblasts to contract extracellular matrix, a function essential for tissue repair, through induction of de novo protein synthesis. Blockade of the Akt/ phosphoinositide 3-kinase (PI3-kinase) pathway with LY294002 and wortmannin prevents the ability of ET-1 to induce ␣-SMA, ezrin, paxillin, and moesin and to promote matrix contraction. Dominant negative rac and Akt blocked the ability of ET-1 to promote formation of ␣-SMA stress fibers. Using specific ET-1 receptor inhibitors, we show that ET-1 induces collagen matrix contraction through the ETA, but not the ETB, receptor. Relative to normal pulmonary fibroblasts, fibroblasts cultured from scars of patients with the fibrotic disease systemic sclerosis (scleroderma) show enhanced ET-1 expression and binding. Systemic sclerosis lung fibroblasts show increased ability to contract a collagen matrix and elevated expression of the procontractile proteins ␣-SMA, ezrin, paxillin, and moesin, which are greatly reduced by antagonizing endogenous ET-1 signaling. Thus, blocking ET-1 or the PI3-kinase/Akt cascades might be beneficial in reducing scar formation in pulmonary fibrosis. INTRODUCTIONA complex histological and architectural structure is a prerequisite for effective lung function. In the lung, specialized structures, the alveoli, increase the surface area of the lung, allowing for efficient gas exchange. The maintenance of these specialized structures is in turn dependent on the underlying connective tissue, comprised principally of fibroblasts and extracellular matrix (ECM; for review, see Gadek et al., 1984), which is essential for the mechanical and structural integrity of the lung. As a response to environmental insults, or as a consequence of local inflammatory processes, structural damage to the lung can occur, resulting in a wound healing response. This response consists of an integrated series of biochemical, immunological, and structural changes that result in the de novo synthesis of a new epithelium, blood vessels, and connective tissue (Razzaque and Taguchi, 2003). The proper repair of connective tissue requires synthesis of new ECM components, such as collagen and fibronectin (Badylak, 2002). In addition, repair of connective tissue requires the proper reconstitution of its support function; that is, an appropriate tensile strength must be recreated. This tensile strength results from the remodeling of the newly formed ECM through a combination of cell locomotion and translocation of the flexible collage...

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“…The mitogenic effects of ET–1 on benign prostatic smooth muscle cells is mediated by both ET receptors [4, 17]. In contrast, the effect of ET–1 on prostate cancer cell proliferation is ET A receptor–dependent.…”

Section: Discussionmentioning

confidence: 99%

Autoradiographic Localisation and Contractile Properties of Prostatic Endothelin Receptors in Patients with Bladder Outlet Obstruction

Mumtaz

Dashwood²,

Thompson³

et al. 2001

European Urology

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Mitogenic activity of endothelin on human cultured prostatic smooth muscle cells

Cited by 30 publications

References 27 publications

Release of vasoactive substances from endothelial cells by shear stress and purinergic mechanosensory transduction

Release of vasoactive substances from endothelial cells by shear stress and purinergic mechanosensory transduction

Endothelin-1 Promotes Myofibroblast Induction through the ETA Receptor via a rac/Phosphoinositide 3-Kinase/Akt-dependent Pathway and Is Essential for the Enhanced Contractile Phenotype of Fibrotic Fibroblasts

Autoradiographic Localisation and Contractile Properties of Prostatic Endothelin Receptors in Patients with Bladder Outlet Obstruction

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