scholarly journals Intratracheal Keratinocyte Growth Factor Enhances Surfactant Protein B Expression in Mechanically Ventilated Preterm Pigs

2021 ◽  
Vol 9 ◽  
Author(s):  
Ramesh Krishnan ◽  
Esmond L. Arrindell ◽  
Caminita Frank ◽  
Zhang Jie ◽  
Randal K. Buddington
Keyword(s):  
Mechanical Ventilation ◽  
Growth Factor ◽  
Epithelial To Mesenchymal Transition ◽  
Keratinocyte Growth Factor ◽  
Surfactant Protein ◽  
Mesenchymal Transition ◽  
Ventilator Induced Lung Injury ◽  
Surfactant Protein B ◽  
Surfactant Production ◽  
Protein B

Bronchopulmonary dysplasia (BPD) is a devastating disease of prematurity that is associated with mechanical ventilation and hyperoxia. We used preterm pigs delivered at gestational day 102 as a translational model for 26–28-week infants to test the hypothesis administering recombinant human keratinocyte growth factor (rhKGF) at initiation of mechanical ventilation will stimulate type II cell proliferation and surfactant production, mitigate ventilator induced lung injury, and reduce epithelial to mesenchymal transition considered as a precursor to BPD. Newborn preterm pigs were intubated and randomized to receive intratracheal rhKGF (20 μg/kg; n = 6) or saline (0.5 ml 0.9% saline; control; n = 6) before initiating 24 h of ventilation followed by extubation to nasal oxygen for 12 h before euthanasia and collection of lungs for histopathology and immunohistochemistry to assess expression of surfactant protein B and markers of epithelial to mesenchymal transition. rhKGF pigs required less oxygen during mechanical ventilation, had higher tidal volumes at similar peak pressures indicative of improved lung compliance, and survival was higher after extubation (83% vs. 16%). rhKGF increased surfactant protein B expression (p < 0.05) and reduced TGF-1β (p < 0.05), that inhibits surfactant production and is a prominent marker for epithelial to mesenchymal transition. Our findings suggest intratracheal administration of rhKGF at initiation of mechanical ventilation enhances surfactant production, reduces ventilator induced lung injury, and attenuates epithelial-mesenchymal transition while improving pulmonary functions. rhKGF is a potential therapeutic strategy to mitigate pulmonary responses of preterm infants that require mechanical ventilation and thereby reduce the incidence and severity of bronchopulmonary dysplasia.

scholarly journals Intratracheal Keratinocyte Growth Factor Enhances Surfactant Protein B Expression in Mechanically Ventilated Preterm Pigs

2021 ◽  
Author(s):  
Ramesh Krishnan ◽  
Esmond Arrindell ◽  
Frank Caminita ◽  
Jie Zhang ◽  
Randal Buddington
Keyword(s):  
Growth Factor ◽  
Lung Injury ◽  
Bronchopulmonary Dysplasia ◽  
Epithelial To Mesenchymal Transition ◽  
Keratinocyte Growth Factor ◽  
Surfactant Protein ◽  
Mesenchymal Transition ◽  
Ventilator Induced Lung Injury ◽  
Human Keratinocyte ◽  
Surfactant Protein B

Abstract Background: Bronchopulmonary dysplasia is a devastating disease of the premature newborn with high morbidity and mortality. Surfactant deficient preterm lungs are susceptible to ventilator induced lung injury, thereby developing bronchopulmonary dysplasia. Despite surfactant therapy and newer ventilation strategies, associated morbidity and mortality remains unchanged. Enhancing surfactant production and reducing ventilator induced lung injury in premature infants are critical. Recombinant keratinocyte growth factor previously been studied to treat adult respiratory distress syndrome. We hypothesized that administering recombinant human keratinocyte growth factor when initiating mechanical ventilation would help stimulate type II cell proliferation and surfactant production. Recombinant human keratinocyte growth factor may also help mitigate ventilator induced lung injury hereby reducing epithelial to mesenchymal transition, a possible precursor to later development of bronchopulmonary dysplasia. Methods: To test our hypothesis, we delivered preterm pigs via cesarean section on day 102. We performed intubation and ventilation for 24 hr. using intermittent positive pressure ventilation. After ventilation began, pigs randomly received intratracheal recombinant human keratinocyte growth factor (20 µg/kg; n=6) or sham treatment (0.5 ml 0.9% saline; n= 6). We recorded physiology data and arterial blood gases during ventilation. After 24 hr. pigs were extubated and received oxygen via nasal cannulation 12 hr. before euthanasia to collect lungs for histopathology and immunohistochemistry. Immunohistochemistry staining was graded and analyzed for surfactant protein B and epithelial to mesenchymal transition markers. Data were analyzed using t-test and Fisher’s exact test. Continuous variables analyzed using ANOVA.Results: Compared with control pigs, recombinant human keratinocyte growth factor pretreated pigs had improved ventilation with higher tidal volumes and required less oxygen (FiO2) during mechanical ventilation for similar peak pressures demonstrating improved lung compliance. Recombinant human keratinocyte growth factor pretreated pig lungs showed increased surfactant protein B expression (p< 0.05) and significantly reduced TGF-β (p< 0.05), a prominent marker for epithelial to mesenchymal transition.Conclusions: Intratracheal recombinant human keratinocyte growth factor administered at initiation of mechanical ventilation enhances surfactant production, reduce lung injury by mitigation of the changes by epithelial mesenchymal transition, thereby improving outcomes. Thus, recombinant human keratinocyte growth factor may represent a potential therapeutic strategy to prevent bronchopulmonary dysplasia.

scholarly journals Intratracheal Keratinocyte Growth Factor Enhances Surfactant Protein B Expression in Mechanically Ventilated Preterm Pigs

2020 ◽  
Author(s):  
Ramesh Krishnan ◽  
Esmond Arrindell ◽  
Frank Caminita ◽  
Jie Zhang ◽  
Randal Buddington
Keyword(s):  
Growth Factor ◽  
Lung Injury ◽  
Bronchopulmonary Dysplasia ◽  
Epithelial To Mesenchymal Transition ◽  
Keratinocyte Growth Factor ◽  
Surfactant Protein ◽  
Mesenchymal Transition ◽  
Ventilator Induced Lung Injury ◽  
Human Keratinocyte ◽  
Surfactant Protein B

Abstract Background: Bronchopulmonary dysplasia is a devastating disease of the premature newborn with high morbidity and mortality. Surfactant deficient preterm lungs are susceptible to ventilator induced lung injury, thereby developing bronchopulmonary dysplasia. Despite surfactant therapy and newer ventilation strategies, associated morbidity and mortality remains unchanged. Enhancing surfactant production and reducing ventilator induced lung injury in premature infants are critical. Recombinant keratinocyte growth factor previously been studied to treat adult respiratory distress syndrome. We hypothesized that administering recombinant human keratinocyte growth factor when initiating mechanical ventilation would help stimulate type II cell proliferation and surfactant production. Recombinant human keratinocyte growth factor may also help mitigate ventilator induced lung injury hereby reducing epithelial to mesenchymal transition, a possible precursor to later development of bronchopulmonary dysplasia. Methods: To test our hypothesis, we delivered preterm pigs via cesarean section on day 102. We performed intubation and ventilation for 24 hr. using intermittent positive pressure ventilation. After ventilation began, pigs randomly received intratracheal recombinant human keratinocyte growth factor (20 μg/kg; n=6) or sham treatment (0.5 ml 0.9% saline; n= 6). We recorded physiology data and arterial blood gases during ventilation. After 24 hr. pigs were extubated and received oxygen via nasal cannulation 12 hr. before euthanasia to collect lungs for histopathology and immunohistochemistry. Immunohistochemistry staining was graded and analyzed for surfactant protein B and epithelial to mesenchymal transition markers. Data were analyzed using t-test and Fisher’s exact test. Continuous variables analyzed using ANOVA.Results: Compared with control pigs, recombinant human keratinocyte growth factor pretreated pigs had improved ventilation with higher tidal volumes and required less oxygen (FiO2) during mechanical ventilation for similar peak pressures demonstrating improved lung compliance. Recombinant human keratinocyte growth factor pretreated pig lungs showed increased surfactant protein B expression (p< 0.05) and significantly reduced TGF-β (p< 0.05), a prominent marker for epithelial to mesenchymal transition. Conclusions: Intratracheal recombinant human keratinocyte growth factor administered at initiation of mechanical ventilation enhances surfactant production, reduce lung injury by mitigation of the changes by epithelial mesenchymal transition, thereby improving outcomes. Thus, recombinant human keratinocyte growth factor may represent a potential therapeutic strategy to prevent bronchopulmonary dysplasia.

Association of the 1580 (C/T) Polymorphism in the Surfactant Protein B Gene with the Severity of Respiratory Failure after Allogeneic Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1840-1840
Author(s):  
Thomas Illmer ◽  
Catrin Theuser ◽  
Christian Thiede ◽  
Markus Schaich ◽  
Simone Trautmann ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Respiratory Failure ◽  
Allogeneic Transplantation ◽  
Surfactant Protein ◽  
Efficient Treatment ◽  
Non Invasive ◽  
Surfactant Protein B ◽  
Non Invasive Ventilation ◽  
To Receive ◽  
Protein B

Abstract Respiratory failure is a serious early complication confounding the clinical effect of allogeneic stem cell transplantation and early detection may be crucial for efficient treatment. We introduced a system of intensive oxigenation monitoring in patients transplanted in our center between November 2001 and December 2003. All allogeneic transplanted patients were followed by a twice daily measurement of oxi-index (paO2/FiO2) during the transplantation period (untill day + 25). Patients that fulfilled criteria of acute lung injury (oxi-index <300) were treated by O2 application vs. non-invasive ventilation (NIV). Failure to increase oxi-index above the threshold of 300 led to referral of the patient to ICU were intensified NIV was applied and/or mechanical ventilation (MV) was initiated based on a defined scoring system. 165 patients were followed for the development of ALI. 48 (29.1%) developed oxiindices <300 (ALI). Development of ALI predicted for a significantly higher rate of ICU admissions (37.5% vs. 6.8% in non-ALI patients; p<0.001) and MV (20.8 % vs. 1.7 in non-ALI patients; p<0.001). ALI was most commonly diagnosed during the engraftment period but was at diagnosis not associated with other criteria like respiration rate, CRP and tachycardia. Since members of the pulmonary innate immune system may be associated with the development of ALI and ARDS we screened the 165 patients for the presence of alternative alleles in the Surfactant Protein B (SP-B) gene. A polymorphism at position +1580 (T/C variation) of SP-B has been previously found to be associated with the development of ARDS. Polymorphism of SP-B were not associated with the development of ALI and did not predict for the need of intensified ICU treatment. However, the rate of MV varied considerably. Nine patients with the T/T genotype (9 out of 42, 21.4%) required intubation and mechanical ventilation whereas none of the patients with C/C had to receive MV (0 out of 30; p=0.01).The data indicate that measurement of the oxiindex is an early sensitive parameter of respiratory failure in allogeneic transplantation and that severity of respiratory damage may be predicted by the T allele at the SP-B +1580 site

scholarly journals Mechanical Ventilation Down-Regulates Surfactant Protein A and Keratinocyte Growth Factor Expression in Premature Rabbits

2007 ◽  
Vol 62 (3) ◽  
pp. 277-282 ◽  
Author(s):  
Robert J Digeronimo ◽  
Shamimunisa B Mustafa ◽  
Rita M Ryan ◽  
Zohara Z Sternberg ◽  
Daniel J Ashton ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Growth Factor ◽  
Keratinocyte Growth Factor ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Factor Expression ◽  
Growth Factor Expression

The pathogenic role of surfactant protein B in formation of bronchopulmonary pathology in children

2017 ◽  
pp. 66-71
Author(s):  
O. Yablon ◽  
◽  
N. Zaichko ◽  
O. Mazulov ◽  
Z.I. Rossokha ◽  
...  
Keyword(s):  
Surfactant Protein ◽  
Pathogenic Role ◽  
Surfactant Protein B ◽  
Protein B

scholarly journals Roles of microRNAs in Regulating Cancer Stemness in Head and Neck Cancers

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1742
Author(s):  
Melysa Fitriana ◽  
Wei-Lun Hwang ◽  
Pak-Yue Chan ◽  
Tai-Yuan Hsueh ◽  
Tsai-Tsen Liao
Keyword(s):  
Growth Factor ◽  
Head And Neck ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Epithelial To Mesenchymal Transition ◽  
Survival Rates ◽  
Growth Factor Receptor ◽  
Cancer Stemness ◽  
Mesenchymal Transition

Head and neck squamous cell carcinomas (HNSCCs) are epithelial malignancies with 5-year overall survival rates of approximately 40–50%. Emerging evidence indicates that a small population of cells in HNSCC patients, named cancer stem cells (CSCs), play vital roles in the processes of tumor initiation, progression, metastasis, immune evasion, chemo-/radioresistance, and recurrence. The acquisition of stem-like properties of cancer cells further provides cellular plasticity for stress adaptation and contributes to therapeutic resistance, resulting in a worse clinical outcome. Thus, targeting cancer stemness is fundamental for cancer treatment. MicroRNAs (miRNAs) are known to regulate stem cell features in the development and tissue regeneration through a miRNA–target interactive network. In HNSCCs, miRNAs act as tumor suppressors and/or oncogenes to modulate cancer stemness and therapeutic efficacy by regulating the CSC-specific tumor microenvironment (TME) and signaling pathways, such as epithelial-to-mesenchymal transition (EMT), Wnt/β-catenin signaling, and epidermal growth factor receptor (EGFR) or insulin-like growth factor 1 receptor (IGF1R) signaling pathways. Owing to a deeper understanding of disease-relevant miRNAs and advances in in vivo delivery systems, the administration of miRNA-based therapeutics is feasible and safe in humans, with encouraging efficacy results in early-phase clinical trials. In this review, we summarize the present findings to better understand the mechanical actions of miRNAs in maintaining CSCs and acquiring the stem-like features of cancer cells during HNSCC pathogenesis.

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