Lung regeneration and translational implications of the postpneumonectomy model

Thane, Kristen E.; Ingenito, Edward P.; Hoffman, Andrew M.

doi:10.1016/j.trsl.2013.11.010

Cited by 26 publications

(24 citation statements)

References 133 publications

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“…New alveolar tissue is preferentially laid down at the periphery of the lung (Foster et al, 2002; Massaro and Massaro, 1993) where mechanical strain of the septa is accentuated due to a relative lack of bronchovascular support (Yilmaz et al, 2011). Evidence exists for proliferation and changes in the behavior of multiple cell lineages in the PNX model, including bronchiolar cells, AEC2s, endothelial cells and Pdgfrα+ stromal cells (Chen et al, 2012b; Eisenhauer et al, 2013; Hoffman et al, 2010; Hsia, 2004; Thane et al, 2014; Voswinckel et al, 2004). …”

Section: Remodeling and Regrowth Of The Alveolar Region After Pneumonmentioning

confidence: 99%

“…Elucidation of the mechanisms that drive regrowth, and how they are attenuated as lung capacity is restored, may suggest potential therapeutic interventions for when repair does not occur properly. However, it will first be important to translate findings with small rodent models to larger animal models with different mechanical and growth conditions in their lungs (Hsia, 2004; Thane et al, 2014). …”

Section: Remodeling and Regrowth Of The Alveolar Region After Pneumonmentioning

confidence: 99%

See 1 more Smart Citation

Repair and Regeneration of the Respiratory System: Complexity, Plasticity, and Mechanisms of Lung Stem Cell Function

Hogan¹,

Barkauskas²,

et al. 2014

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Respiratory disease is the third leading cause of death in the industrialized world. Consequently, the trachea, lungs, and cardiopulmonary vasculature have been the focus of extensive investigations. Recent studies have provided new information about the mechanisms driving lung development and differentiation. However, there is still much to learn about the ability of the adult respiratory system to undergo repair and to replace cells lost in response to injury and disease. This review highlights the multiple stem/progenitor populations in different regions of the adult lung, the plasticity of their behavior in injury models, and molecular pathways that support homeostasis and repair.

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Section: Remodeling and Regrowth Of The Alveolar Region After Pneumonmentioning

confidence: 99%

Section: Remodeling and Regrowth Of The Alveolar Region After Pneumonmentioning

confidence: 99%

Repair and Regeneration of the Respiratory System: Complexity, Plasticity, and Mechanisms of Lung Stem Cell Function

Hogan¹,

Barkauskas²,

et al. 2014

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“…This is perhaps best exemplified by the regenerative neo-alveolarization that occurs following unilateral pneumonectomy in small rodents. In these models, the removal of a single lung invokes a rapid period of compensatory growth in the remaining lung characterized by the re-expression of growth factors and extracellular matrix components produced during developmental alveolarization, and the proliferation of pulmonary epithelial and endothelial cells, resulting in a complete restoration of total lung capacity [68]. Mechanical stretch of the remaining lung and increased pulmonary blood flow have been hypothesized as initiating factors in invoking this compensatory growth, thought to occur via increases in both alveolar number and size of existing alveoli [69,70].…”

Section: Overview Of Lung Developmentmentioning

confidence: 99%

Disrupted lung development and bronchopulmonary dysplasia

Baker¹,

Alvira

2014

Current Opinion in Pediatrics

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Purpose of review Advances of medical therapy have increased survival of extremely premature infants, and changed the pathology of bronchopulmonary dysplasia (BPD) from one of acute lung injury to a disease of disrupted lung development. With this evolution, new questions emerge regarding: (i) the molecular mechanisms that control postnatal lung development; (ii) the effect of early disruptions of postnatal lung development on long-term lung function; and (iii) the existence of endogenous mechanisms that permit lung regeneration after injury. Recent Findings Recent data demonstrate that a significant component of alveolarization, the final stage of lung development, occurs postnatally. Further, clinical and experimental studies demonstrate that premature birth disrupts alveolarization, decreasing the gas exchange surface area of the lung and causing BPD. BPD is associated with significant short-term morbidity, and new longitudinal, clinical data demonstrate that survivors of BPD have long-standing deficits in lung function, and may be at risk for the development of additional lung disease as adults. Unfortunately, current care is mainly supportive with few effective therapies that prevent or treat established BPD. These studies underscore the need to further elucidate the mechanisms that direct postnatal lung growth, and develop innovative strategies to stimulate lung regeneration. Summary Despite significant improvements in the care and survival of extremely premature infants, BPD remains a major clinical problem. While efforts should remain focused on the prevention of preterm labor and BPD, novel research aimed at promoting postnatal alveolarization offers a unique opportunity to develop effective strategies to treat established BPD.

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“…In many species, including mice, dogs, and humans, compensatory and regenerative growth occurs in the remaining lung tissues following PNX (Butler et al, 2012;Thane et al, 2014;Hsia et al, 1994). Mechanical stress has been assumed to be one of the most important initiating factors in post-PNX alveolar regeneration (Thane et al, 2014). However, the cellular responses of alveolar stem cells to the increased mechanical tension are as yet uncharacterized.…”

Section: Introductionmentioning

confidence: 99%

MAPK-Mediated YAP Activation Controls Mechanical-Tension-Induced Pulmonary Alveolar Regeneration

et al. 2016

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The pulmonary alveolar epithelium undergoes extensive regeneration in response to lung injuries, including lung resection. In recent years, our understanding of cell lineage relationships in the pulmonary alveolar epithelium has improved significantly. However, the molecular and cellular mechanisms that regulate pneumonectomy (PNX)-induced alveolar regeneration remain largely unknown. In this study, we demonstrate that mechanical-tension-induced YAP activation in alveolar stem cells plays a major role in promoting post-PNX alveolar regeneration. Our results indicate that JNK and p38 MAPK signaling is critical for mediating actin-cytoskeleton-remodeling-induced nuclear YAP expression in alveolar stem cells. Moreover, we show that Cdc42-controlled actin remodeling is required for the activation of JNK, p38, and YAP in post-PNX lungs. Our findings together establish that the Cdc42/F-actin/MAPK/YAP signaling cascade is essential for promoting alveolar regeneration in response to mechanical tension in the lung.

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Lung regeneration and translational implications of the postpneumonectomy model

Cited by 26 publications

References 133 publications

Repair and Regeneration of the Respiratory System: Complexity, Plasticity, and Mechanisms of Lung Stem Cell Function

Repair and Regeneration of the Respiratory System: Complexity, Plasticity, and Mechanisms of Lung Stem Cell Function

Disrupted lung development and bronchopulmonary dysplasia

MAPK-Mediated YAP Activation Controls Mechanical-Tension-Induced Pulmonary Alveolar Regeneration

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