Mechanical Stretch Increases Secretion of Parathyroid Hormone-Related Protein by Cultured Bladder Smooth Muscle Cells

Steers, William D.; Broder, Stanford R.; Persson, Katarina; Bruns, David E.; Ferguson, James E.; Bruns, M E; Tuttle, Jeremy B.

doi:10.1016/s0022-5347(01)62831-3

Cited by 30 publications

(17 citation statements)

References 21 publications

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“…Fibroblasts were maintained in DMEM/10% FBS or DMEM/0.1% bovine serum albumin (BSA) until further processing. These cells were LFs based on vimentin staining (Ͼ95% positive), and all the cells contained neutral lipid pools by electron microscopy (29).…”

Section: Methodsmentioning

confidence: 98%

Stretch-stimulated surfactant synthesis is coordinated by the paracrine actions of PTHrP and leptin

Torday

Rehan²

2002

American Journal of Physiology-Lung Cellular and Molecular Phys

127

146

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Torday, J. S., and V. K. Rehan. Stretch-stimulated surfactant synthesis is coordinated by the paracrine actions of PTHrP and leptin. Am J Physiol Lung Cell Mol Physiol 283: L130-L135, 2002. First published February 22, 2002; 10.1152/ajplung.00380.2001.-Intrauterine lung development, culminating in physiological pulmonary surfactant production by epithelial type II (TII) cells, is driven by fluid distension through unknown mechanisms. Differentiation of alveolar epithelial and mesenchymal cells is mediated by soluble factors like parathyroid hormone-related protein (PTHrP), a stretch-sensitive TII cell product. PTHrP stimulates pulmonary surfactant production by a paracrine feedback loop mediated by leptin, a soluble product of the mature lipofibroblast (LF). When LFs and TIIs are stretched in coculture, there is a fivefold increase in surfactant phospholipid synthesis that can be "neutralized" by inhibitors of PTHrP or leptin, implicating a paracrine feedback loop in this mechanism. Stretching LFs stimulates PTHrP binding (2.5-fold) and downstream stimulation of triglyceride uptake quantitatively (15-25%) due to upregulation of adipose differentiation-related protein expression. Stretching TII cells increases leptin stimulation of their surfactant phospholipid synthesis threefold, suggesting that retrograde signaling by leptin to TII cells is also stretch sensitive. We conclude that the effect of stretch on alveolar LF and TII differentiation is coordinated by PTHrP, leptin, and their receptors.lipofibroblast; parathyroid hormone-related protein; leptin; adipose differentiation-related protein INTRAUTERINE LUNG DEVELOPMENT is driven by lung fluid secretion, which distends the alveolar acinus, forming a "bubblelike" template for its structure and function (2, 16). Stretch stimulates the growth and differentiation of both the epithelial and mesenchymal cells of the alveolar septal wall in preparation for air breathing at the time of birth. Of particular importance to the transition from intrauterine to extrauterine adaptation is the synthesis and secretion of pulmonary surfactant by alveolar type II cells. The surfactant reduces surface tension of the lung lining layer, preventing atelectasis of the air-filled lung. The surfactant is a complex of both proteins and phospholipids, the latter being responsible for the lowering of surface tension.It has previously been shown that stretching stimulates the growth of cultured mixed lung cells (15) and the secretion of pulmonary surfactant phospholipid by epithelial type II (TII) cells (38). It has subsequently been shown that stretch increases the expression of surfactant proteins (27). However, there is no information regarding how stretch stimulates surfactant phospholipid synthesis. Developing TII cell surfactant phospholipid synthesis is controlled by a wide variety of growth factors (13), cytokines (41), and eicosanoids (10), which mediate the paracrine regulation of fetal lung development. Among these, prostaglandin E 2 (PGE 2 ) and parathyroid hormone-related p...

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Section: Methodsmentioning

confidence: 98%

Stretch-stimulated surfactant synthesis is coordinated by the paracrine actions of PTHrP and leptin

Torday

Rehan²

2002

American Journal of Physiology-Lung Cellular and Molecular Phys

127

146

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“…PTHrP mRNA increased substantially with distension of the bladder, and in vitro, PTHrP-1(1-34)-NH 2 relaxed carbachol-induced contractions in strips from bladders kept empty in vivo. To test whether PTHrP could be increased solely by stretch rather than other possible in vivo variables, Steers et al (1998) stretched cultured bladder smooth muscle cells and analyzed the culture medium for the protein. In response to mechanical stretch, PTHrP was increased in the smooth muscle cell cultures.…”

Section: Peripheral Targetsmentioning

confidence: 99%

“…PTHrP (1-100 nM) relaxed carbachol-contracted bladder body, but it did not affect bladder contractions induced by KCl (124 mM) or ␣,␤-methylene ATP (10 M). Steers et al (1998) suggested the possibility that increased PTHrP secretion in response to stretching of smooth muscle can be an autocrine action to relax the bladder during filling. However, PTHrP may also exert a paracrine action on vessels regulating blood flow during bladder filling or it may modulate neural activity.…”

Section: Peripheral Targetsmentioning

confidence: 99%

Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence

Andersson

Wein²

2004

Pharmacol Rev

453

364

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“…Steers et al [26] showed that, in response to mechanical stretch, PTHrP was increased in bladder cell culture. In the same study, it was suggested that PTHrP has an autocrine action to relax the bladder during filling, and that it may also exert a paracrine action on the vessels regulating the blood flow during bladder filling.…”

Section: Discussionmentioning

confidence: 99%

Expression of Parathyroid-Hormone- Related Protein in the Partially Obstructed Rabbit Bladder

Pérez-Martínez¹,

Mannikarottu²,

Güven³

et al. 2008

Urol Int

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Introduction: Parathyroid-hormone-related protein (PTHrP) is considered as an autocrine/paracrine regulator of growth and/or differentiation in normal and malignant tissues. We determined the distribution and density of the expression of PTHrP in the rabbit bladder during growth in response to partial outlet obstruction and its relation with the smooth muscle/collagen ratio. Materials and Methods: A total of 30 male New Zealand White rabbits were studied. After 7, 14, 28 or 56 days of obstruction, 6 rabbits per group were sacrificed and the bladder extracted. Six sham-operated rabbits served as controls. The expression and localization of PTHrP or collagen type III were detected by immunohistochemistry using specific antibodies. Results: The levels of PTHrP were progressively increased by 14 days of obstruction, whereas they decreased after 14 days, although the PTHrP positivity was higher than in sham controls by 28 and 56 days of obstruction. PTHrP staining was related to the smooth muscle/collagen ratio, both showing a peak in rabbits obstructed for 14 days. Conclusions: These data indicate that PTHrP may play an important regulatory role in the cellular and vascular response to partial outlet obstruction.

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Mechanical Stretch Increases Secretion of Parathyroid Hormone-Related Protein by Cultured Bladder Smooth Muscle Cells

Cited by 30 publications

References 21 publications

Stretch-stimulated surfactant synthesis is coordinated by the paracrine actions of PTHrP and leptin

Stretch-stimulated surfactant synthesis is coordinated by the paracrine actions of PTHrP and leptin

Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence

Expression of Parathyroid-Hormone- Related Protein in the Partially Obstructed Rabbit Bladder

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