Surfactant Protein-C in the Maintenance of Lung Integrity and Function

Glasser, Stephan W.

doi:10.4172/2155-6121.s7-001

Cited by 9 publications

(13 citation statements)

References 78 publications

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“…The impairment of the regulation of such genes results in lethal neonatal respiratory distress in mice and humans (reviewed in ref. 26 ). During organogenesis, the earliest surfactant protein of the pre-type II cells is SP-C that, being expressed exclusively in the alveolar type II cells, is considered the most specific marker of appropriate alveolar maturation and successful remodeling of the lung (reviewed in ref.…”

Section: Resultsmentioning

confidence: 99%

Double knock-out of Hmga1 and Hipk2 genes causes perinatal death associated to respiratory distress and thyroid abnormalities in mice

et al. 2019

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The serine–threonine kinase homeodomain-interacting protein kinase 2 (HIPK2) modulates important cellular functions during development, acting as a signal integrator of a wide variety of stress signals, and as a regulator of transcription factors and cofactors. We have previously demonstrated that HIPK2 binds and phosphorylates High-Mobility Group A1 (HMGA1), an architectural chromatinic protein ubiquitously expressed in embryonic tissues, decreasing its binding affinity to DNA. To better define the functional role of HIPK2 and HMGA1 interaction in vivo, we generated mice in which both genes are disrupted. About 50% of these Hmga1/Hipk2 double knock-out (DKO) mice die within 12 h of life (P1) for respiratory failure. The DKO mice present an altered lung morphology, likely owing to a drastic reduction in the expression of surfactant proteins, that are required for lung development. Consistently, we report that both HMGA1 and HIPK2 proteins positively regulate the transcriptional activity of the genes encoding the surfactant proteins. Moreover, these mice display an altered expression of thyroid differentiation markers, reasonably because of a drastic reduction in the expression of the thyroid-specific transcription factors PAX8 and FOXE1, which we demonstrate here to be positively regulated by HMGA1 and HIPK2. Therefore, these data indicate a critical role of HIPK2/HMGA1 cooperation in lung and thyroid development and function, suggesting the potential involvement of their impairment in the pathogenesis of human lung and thyroid diseases.

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Section: Resultsmentioning

confidence: 99%

Double knock-out of Hmga1 and Hipk2 genes causes perinatal death associated to respiratory distress and thyroid abnormalities in mice

et al. 2019

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“…While SP-C confers dramatic surface activity it is not essential for perinatal transition to breathing. Individuals lacking SP-C survive but develop a variety of interstitial or fibrotic lung disease outcomes [1]. SP-C related disease can occur as acute postnatal respiratory distress or with slow onset that is identified as respiratory insufficiency during childhood through adulthood [2,3].…”

Section: Introductionmentioning

confidence: 99%

“…Respiratory crises in affected SFTPC individuals have been linked to viral infections that include influenza, parainfluenza, and RSV [1,9,10]. RSV is a common pediatric respiratory pathogen that elicits an intense inflammatory injury primarily in infants but can also re-infect and complicate adult chronic obstructive pulmonary disease (COPD).…”

Section: Introductionmentioning

confidence: 99%

Genetic replacement of surfactant protein-C reduces respiratory syncytial virus induced lung injury

et al. 2013

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BackgroundIndividuals with deficiencies of pulmonary surfactant protein C (SP-C) develop interstitial lung disease (ILD) that is exacerbated by viral infections including respiratory syncytial virus (RSV). SP-C gene targeted mice (Sftpc -/-) lack SP-C, develop an ILD-like disease and are susceptible to infection with RSV.MethodsIn order to determine requirements for correction of RSV induced injury we have generated compound transgenic mice where SP-C expression can be induced on the Sftpc -/- background (SP-C/Sftpc -/-) by the administration of doxycycline (dox). The pattern of induced SP-C expression was determined by immunohistochemistry and processing by Western blot analysis. Tissue and cellular inflammation was measured following RSV infection and the RSV-induced cytokine response of isolated Sftpc +/+ and -/- type II cells determined.ResultsAfter 5 days of dox administration transgene SP-C mRNA expression was detected by RT-PCR in the lungs of two independent lines of bitransgenic SP-C/Sftpc -/- mice (lines 55.3 and 54.2). ProSP-C was expressed in the lung, and mature SP-C was detected by Western blot analysis of the lavage fluid from both lines of SP-C/Sftpc -/- mice. Induced SP-C expression was localized to alveolar type II cells by immunostaining with an antibody to proSP-C. Line 55.3 SP-C/Sftpc -/- mice were maintained on or off dox for 7 days and infected with 2.6x107 RSV pfu. On day 3 post RSV infection total inflammatory cell counts were reduced in the lavage of dox treated 55.3 SP-C/Sftpc -/- mice (p = 0.004). The percentage of neutrophils was reduced (p = 0.05). The viral titers of lung homogenates from dox treated 55.3 SP-C/Sftpc -/- mice were decreased relative to 55.3 SP-C/Sftpc -/- mice without dox (p = 0.01). The cytokine response of Sftpc -/- type II cells to RSV was increased over that of Sftpc +/+ cells.ConclusionsTransgenic restoration of SP-C reduced inflammation and improved viral clearance in the lungs of SP-C deficient mice. The loss of SP-C in alveolar type II cells compromises their response to infection. These findings show that the restoration of SP-C in Sftpc -/- mice in response to RSV infection is a useful model to determine parameters for therapeutic intervention.

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“…Quality world, a small personal world, which each person starts to create in his or her memory shortly after birth and continues to create and re-create throughout life, is made up of specific pictures that portray, more than anything else we know, the best ways to satisfy one or more of our basic needs [3]. Quality world pictures internally create notions of how we would like things to be, and are related to certain basic needs of every human being.…”

Section: Discussionmentioning

confidence: 99%

Discussion of Glasser’s “Quality World” among Medical Students Benefited Group Dynamics

Hwang¹,

Fan²,

Hwang³

2013

UCMS

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Purpose: The aim of this study is to analyze the Glasser's "Quality World" as it is discussed among the medical students and to see if there is any relationship between it and their academic/creativity scores. It also seeks if this discussion is of any benefit to the group dynamics. Methods: Participants were 205 medical students, 4 to 7 students were allocated as a group. They were asked to fill an open answer to 4 categories of "Quality World" (the people we most want to be with, the things we most want to own or experience, the idea or system of belief that govern much of our behavior, and the places we most want to visit or live) and discuss them in an open forum. Torrance Tests of Creative Thinking were performed to the students. They answered the Likert scale question whether discussing the "Quality World" with peers benefited the group dynamics or not. Results: Among 205 students, 50.2% wanted to be with adoring people; followed by entertainers and artists (18%), 51.7% wanted to own material wealth; spiritual values were second in importance (21%), 27.3% considered family, friends, and lovers most valuable; followed by happiness (21%), 52.2% wished for an overseas trip; trip to the mountains, seas, or deserts was next in importance (14.1%). Most of the respondents answered that discussing "Quality World" benefited their group dynamics. Conclusion: We suggest that discussing Glasser's "Quality World" might be a useful tool to gain understanding among the health personnel in small group activities and increase group dynamics.

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Surfactant Protein-C in the Maintenance of Lung Integrity and Function

Cited by 9 publications

References 78 publications

Double knock-out of Hmga1 and Hipk2 genes causes perinatal death associated to respiratory distress and thyroid abnormalities in mice

Double knock-out of Hmga1 and Hipk2 genes causes perinatal death associated to respiratory distress and thyroid abnormalities in mice

Genetic replacement of surfactant protein-C reduces respiratory syncytial virus induced lung injury

Discussion of Glasser’s “Quality World” among Medical Students Benefited Group Dynamics

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