COMPENSATORY LUNG GROWTH: LUNG PROTEIN,DNA AND RNA CONTENTS IN TRILOBECTOMIZED RATS

Aiming at assessing compensatory lung growth after trilobectomy in rats, 3 groups of animals (control, thoracotomy and trilobectomy) were studied over 3 time intervals (7, 30 and 180 days post-operation). Protein, DNA and RNA contents in each lung were evaluated. The study of the left lung protein content reveals that compensatory growth ceased by day 30, whereas it continued to occur in the cranial lobe as long as 180 days post-operation. The lung DNA content in trilobectomized animals remained smaller than in the animals of the other groups demonstrating that compensatory growth was not brought about by hyperplasia. The lung RNA content in trilobectomized animals increased similarly to the lung protein content, demonstrating that the cells of the lung tissue must have had an increase in volume as no significant increase in their number occurred, as shown by the analysis of the lung DNA content. Therefore, it may be concluded that, in our experiment with adult animals, compensatory lung growth after trilobectomy in rats occurred due to an increase in the lung protein content and RNA content, suggesting a cellular volume increase (hypertrophy) and a probable increase in the intralveolar septs rather than an important cell multiplication

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Compensatory lung growth: protein, DNA and RNA lung contents in undernourished trilobectomized rats

Acta Cirurgica Brasileira ◽

10.1590/s0102-86502005000300005 ◽

2005 ◽

Vol 20 (3) ◽

pp. 219-224

Author(s):

Raul Lopes Ruiz Júnior ◽

Lídia Raquel de Carvalho ◽

Antonio José Maria Cataneo

Keyword(s):

Small Rna ◽

Left Lung ◽

Lung Growth ◽

Cell Hyperplasia ◽

Adult Rats ◽

Compensatory Lung Growth ◽

Dna And Rna ◽

Male Wistar Rats ◽

ON THE METABOLIC ACTION OF TESTOSTERONE AND RELATED COMPOUNDS

Acta Endocrinologica ◽

10.1530/acta.0.0390223 ◽

1962 ◽

Vol 39 (2) ◽

pp. 223-233 ◽

Cited By ~ 24

Author(s):

A. Kassenaar ◽

A. Kouwenhoven ◽

A. Querido

Keyword(s):

Dna Content ◽

Seminal Vesicles ◽

List Type ◽

Substitution Therapy ◽

Kidney Weight ◽

Dna And Rna ◽

Rna Content ◽

Metabolic Action ◽

Related Compounds ◽

Rna Concentration

ABSTRACT 1. Changes in nucleic acid composition of the seminal vesicles and kidneys of mice which occur after castration and after substitution therapy with testosterone in castrated animals were studied. 2. It was found that after castration both the DNA and RNA content of the seminal vesicles decreases. The concentration of DNA, however, increases while the RNA concentration in this tissue decreases. 3. These changes are reversed by treatment with testosterone. The rise in RNA content precedes the increase in DNA content of this organ. 4. No changes in DNA content of the kidneys were found either after castration or after treatment with testosterone of castrated mice. The RNA content of this organ changed parallel with the changes in weight. 5. These results strongly suggest that with testosterone treatment, the growth of the seminal vesicles is due to hyperplasia as well as hypertrophy, while the increase in kidney weight is due only to hypertrophy.

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Effect of lung collapse on compensatory lung growth

Journal of Applied Physiology ◽

10.1152/jappl.1977.43.1.27 ◽

1977 ◽

Vol 43 (1) ◽

pp. 27-31 ◽

Cited By ~ 10

Author(s):

L. S. Inselman ◽

R. B. Mellins ◽

J. A. Brasel

Keyword(s):

Left Lung ◽

Lung Growth ◽

Lung Collapse ◽

Halothane Anesthesia ◽

Adult Rat ◽

Compensatory Lung Growth ◽

Contralateral Lung ◽

Old Adult ◽

Old Rats ◽

Long Evans

The effect of unilateral lung collapse on compensatory lung growth was studied in 3-wk-old (young) and 10-wk-old (adult) male Long-Evans rats. Under light halothane anesthesia, left lung collapse was produced by injection of dental plastic through a thracheostomy cannula. The rats were killed either 5 days or 4 wk later. At 5 days postcollapse, the 3-wk-old rats had an increase in DNA over sham controls (21%) (P less than 0.05), with no significant change in the protein/DNA ratio. At 4 wk postcollapse, increases in DNA over shamoperated controls were observed in both the 3-wk-old (58%) and the 10-wk-old (28%) rats, whereas the protein/DNA ratio at both ages was significantly less than that of sham controls (P less than 0.05). Thus, unilateral lung collapse stimulates growth of the contralateral lung by cellular hyperplasia, not hypertrophy, both in the young and adult rat. The hyperplasia begins within 5 days after collapse and is greater by 4 wk. The extent of hyperplasia is greater in the young than in the adult rat.

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Localization and stretch-dependence of lung elastase activity in development and compensatory growth

Journal of Applied Physiology ◽

10.1152/japplphysiol.00954.2014 ◽

2015 ◽

Vol 118 (7) ◽

pp. 921-931 ◽

Cited By ~ 11

Author(s):

Sarah Marie Young ◽

Sheng Liu ◽

Rashika Joshi ◽

Matthew R. Batie ◽

Matthew Kofron ◽

...

Keyword(s):

Ex Vivo ◽

Left Lung ◽

Mouse Lung ◽

Matrix Remodeling ◽

Lung Growth ◽

Elastase Activity ◽

Compensatory Lung Growth ◽

The Matrix ◽

Applied Forces ◽

Lung Matrix

Synthesis and remodeling of the lung matrix is necessary for primary and compensatory lung growth. Because cyclic negative force is applied to developing lung tissue during the respiratory cycle, we hypothesized that stretch is a critical regulator of lung matrix remodeling. By using quantitative image analysis of whole-lung and whole-lobe elastin in situ zymography images, we demonstrated that elastase activity increased twofold during the alveolar stage of postnatal lung morphogenesis in the mouse. Remodeling was restricted to alveolar walls and ducts and was nearly absent in dense elastin band structures. In the mouse pneumonectomy model of compensatory lung growth, elastase activity increased threefold, peaking at 14 days postpneumonectomy and was higher in the accessory lobe compared with other lobes. Remodeling during normal development and during compensatory lung growth was different with increased major airway and pulmonary arterial remodeling during development but not regeneration, and with homogenous remodeling throughout the parenchyma during development, but increased remodeling only in subpleural regions during compensatory lung growth. Left lung wax plombage prevented increased lung elastin during compensatory lung growth. To test whether the adult lung retains an innate capacity to remodel elastin, we developed a confocal microscope-compatible stretching device. In ex vivo adult mouse lung sections, lung elastase activity increased exponentially with strain and in peripheral regions of lung more than in central regions. Our study demonstrates that lung elastase activity is stretch-dependent and supports a model in which externally applied forces influence the composition, structure, and function of the matrix during periods of alveolar septation.

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Inhibition of compensatory lung growth in endothelial nitric oxide synthase-deficient mice

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00490.2001 ◽

2002 ◽

Vol 282 (6) ◽

pp. L1272-L1278 ◽

Cited By ~ 56

Author(s):

Shari M. Leuwerke ◽

Aditya K. Kaza ◽

Curtis G. Tribble ◽

Irving L. Kron ◽

Victor E. Laubach

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Endothelial Nitric Oxide Synthase ◽

Compensatory Growth ◽

Lung Growth ◽

Wild Type ◽

Compensatory Lung Growth ◽

Oxide Synthase ◽

Endothelial Nitric Oxide ◽

Deficient Mice

Pneumonectomy results in rapid compensatory growth of the remaining lung and also leads to increased flow and shear stress, which are known to stimulate endothelial nitric oxide synthase (eNOS). Nitric oxide is an essential mediator of vascular endothelial growth factor-induced angiogenesis, which should necessarily occur during compensatory lung growth. Thus our hypothesis is that eNOS is critical for compensatory lung growth. To test this, left pneumonectomy was performed in eNOS-deficient mice (eNOS−/−), and compensatory growth of the right lung was characterized throughout 14 days postpneumonectomy and compared with wild-type pneumonectomy and sham controls. Compensatory lung growth was severely impaired in eNOS−/− mice, as demonstrated by significant reductions in lung weight index, lung volume index, and volume of respiratory region. Also, pneumonectomy-induced increases in alveolar surface density and cell proliferation were prevented in eNOS−/− mice, indicating that eNOS plays a role in alveolar hyperplasia. Compensatory lung growth was also impaired in wild-type mice treated with the nitric oxide synthase inhibitor N G-nitro-l-arginine methyl ester. Together, these results indicate that eNOS is critical for compensatory lung growth.

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Signals and mechanisms of compensatory lung growth

Journal of Applied Physiology ◽

10.1152/japplphysiol.00530.2004 ◽

2004 ◽

Vol 97 (5) ◽

pp. 1992-1998 ◽

Cited By ~ 71

Author(s):

Connie C. W. Hsia

Keyword(s):

Structure Function ◽

Compensatory Growth ◽

Respiratory Muscles ◽

Normal Structure ◽

Feedback System ◽

Experimental Manipulation ◽

Critical Threshold ◽

Lung Growth ◽

Compensatory Lung Growth ◽

Mechanical Feedback

Growth of the lung involves unique structure-function interactions not seen in solid organs. Mechanical feedback between the lung and thorax constitutes a major signal that sustains developmental as well as compensatory lung growth. After the loss of lung units as by pneumonectomy (PNX), increased mechanical stress and strain on the remaining units induce adaptive responses to augment oxygen transport, including 1) recruitment of alveolar-capillary reserves, 2) remodeling of existing tissue, and 3) regenerative growth of acinar tissue when strain exceeds a critical threshold. Alveolar hypoxia, hormones, and growth factors may feed into the mechanical feedback system to modify an existing growth response but are unlikely to initiate compensatory growth in the absence of sufficient mechanical signals. Whereas endogenous post-PNX alveolar growth preserves normal structure-function relationships, experimental manipulation of selected metabolic pathways can distort these relationships. Finally, PNX widens the disparity between the rapidly adapting acini and slowly adapting conducting airways and blood vessels, leading to disproportionate airflow and hemodynamic dysfunction and secondary hypertrophy of the right ventricle and respiratory muscles that limits overall organ function despite regeneration of gas exchange tissue. These are key concepts to consider when formulating approaches to stimulate or augment compensatory growth in chronic lung disease.

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Partial pneumonectomy of telomerase null mice carrying shortened telomeres initiates cell growth arrest resulting in a limited compensatory growth response

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00409.2010 ◽

2011 ◽

Vol 300 (6) ◽

pp. L898-L909 ◽

Cited By ~ 16

Author(s):

Sha-Ron Jackson ◽

Jooeun Lee ◽

Raghava Reddy ◽

Genevieve N. Williams ◽

Alexander Kikuchi ◽

...

Keyword(s):

Cell Growth ◽

Compensatory Growth ◽

Growth Arrest ◽

Telomerase Activity ◽

Lung Growth ◽

Wild Type ◽

Term Survival ◽

Cell Growth Arrest ◽

Compensatory Lung Growth ◽

The Impact

Telomerase mutations and significantly shortened chromosomal telomeres have recently been implicated in human lung pathologies. Natural telomere shortening is an inevitable consequence of aging, which is also a risk factor for development of lung disease. However, the impact of shortened telomeres and telomerase dysfunction on the ability of lung cells to respond to significant challenge is still largely unknown. We have previously shown that lungs of late generation, telomerase null B6.Cg- Terc tm1Rdp mice feature alveolar simplification and chronic stress signaling at baseline, a phenocopy of aged lung. To determine the role telomerase plays when the lung is challenged, B6.Cg- Terc tm1Rdp mice carrying shortened telomeres and wild-type controls were subjected to partial pneumonectomy. We found that telomerase activity was strongly induced in alveolar epithelial type 2 cells (AEC2) of the remaining lung immediately following surgery. Eighty-six percent of wild-type animals survived the procedure and exhibited a burst of early compensatory growth marked by upregulation of proliferation, stress response, and DNA repair pathways in AEC2. In B6.Cg- Terc tm1Rdp mice carrying shortened telomeres, response to pneumonectomy was characterized by decreased survival, diminished compensatory lung growth, attenuated distal lung progenitor cell response, persistent DNA damage, and cell growth arrest. Overall, survival correlated strongly with telomere length. We conclude that functional telomerase and properly maintained telomeres play key roles in both long-term survival and the early phase of compensatory lung growth following partial pneumonectomy.

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Role of pulmonary blood flow in postpneumonectomy lung growth

Journal of Applied Physiology ◽

10.1152/jappl.1992.73.6.2448 ◽

1992 ◽

Vol 73 (6) ◽

pp. 2448-2451 ◽

Cited By ~ 16

Author(s):

J. T. McBride ◽

K. K. Kirchner ◽

G. Russ ◽

J. Finkelstein

Keyword(s):

Blood Flow ◽

Cardiac Output ◽

Pulmonary Blood Flow ◽

Compensatory Growth ◽

Left Lung ◽

Lung Growth ◽

Caudal Lobe ◽

Dna Contents ◽

The Right

To study the influence of blood flow on postpneumonectomy lung growth, we banded the left caudal lobe pulmonary artery of eight ferrets in such a way that blood flow to the caudal lobe did not increase when the right lung was excised 1 wk later. The fraction of the cardiac output received by the right lung before pneumonectomy was therefore directed entirely to the left cranial lobe. Three weeks after pneumonectomy the weight, volume, and protein and DNA contents of the two lobes of the left lung were measured and compared with those of five unoperated animals and eight animals after right pneumonectomy alone. Although its perfusion did not increase after pneumonectomy, the left caudal lobe of banded animals participated in compensatory growth, increasing in weight and protein and DNA contents. Although the cranial lobe of banded animals received 25% more of the cardiac output than the same lobe in pneumonectomized animals, cranial lobe volume and protein and DNA contents in the two groups were similar. Caudal lobes were smaller in banded than in simple pneumonectomized animals and tended to contain less protein, whereas the cranial lobes tended to be heavier. We conclude that increased pulmonary perfusion is not necessary for compensatory lung growth in adult ferrets, but it may modify this response.

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Deformation-induced transitional myofibroblasts contribute to compensatory lung growth

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00383.2016 ◽

2017 ◽

Vol 312 (1) ◽

pp. L79-L88 ◽

Cited By ~ 8

Author(s):

Robert D. Bennett ◽

Alexandra B. Ysasi ◽

Willi L. Wagner ◽

Cristian D. Valenzuela ◽

Akira Tsuda ◽

...

Keyword(s):

Transcriptional Activity ◽

Compensatory Growth ◽

Laser Microdissection ◽

Smooth Muscle Actin ◽

Single Cells ◽

Nerve Transection ◽

Lung Growth ◽

Compensatory Lung Growth ◽

Peripheral Lung ◽

Alveolar Duct

In many mammals, including humans, removal of one lung (pneumonectomy) results in the compensatory growth of the remaining lung. Compensatory growth involves not only an increase in lung size, but also an increase in the number of alveoli in the peripheral lung; however, the process of compensatory neoalveolarization remains poorly understood. Here, we show that the expression of α-smooth muscle actin (SMA)—a cytoplasmic protein characteristic of myofibroblasts—is induced in the pleura following pneumonectomy. SMA induction appears to be dependent on pleural deformation (stretch) as induction is prevented by plombage or phrenic nerve transection ( P < 0.001). Within 3 days of pneumonectomy, the frequency of SMA+ cells in subpleural alveolar ducts was significantly increased ( P < 0.01). To determine the functional activity of these SMA+ cells, we isolated regenerating alveolar ducts by laser microdissection and analyzed individual cells using microfluidic single-cell quantitative PCR. Single cells expressing the SMA ( Acta2) gene demonstrated significantly greater transcriptional activity than endothelial cells or other discrete cell populations in the alveolar duct ( P < 0.05). The transcriptional activity of the Acta2+ cells, including expression of TGF signaling as well as repair-related genes, suggests that these myofibroblast-like cells contribute to compensatory lung growth.

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From Limbs to Lungs: A Newt Perspective on Compensatory Lung Growth

Physiology ◽

10.1152/physiologyonline.1999.14.6.260 ◽

1999 ◽

Vol 14 (6) ◽

pp. 260-267 ◽

Cited By ~ 1

Author(s):

Kirk A. Gilbert ◽

D. Eugene Rannels

Keyword(s):

Compensatory Growth ◽

Lung Resection ◽

Limb Regeneration ◽

Structure And Function ◽

Molecular Pathways ◽

Lung Growth ◽

Compensatory Lung Growth ◽

And Function ◽

Partial Lung Resection ◽

Insight Into

Partial lung resection initiates compensatory growth of remaining lobes to restore pulmonary structure and function. Mechanisms underlying this response are not well defined. This article considers molecular pathways involved in control of amphibian limb regeneration and tissue pattern formation for novel insight into the understanding of compensatory lung growth.

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