The effect of the mechanodynamic lung environment on fibroblast phenotype via the Flexcell DOI Creative Commons

S. Al Yazeedi,

A. F Abokor,

J. Brussow

и другие.

BMC Pulmonary Medicine, Год журнала: 2024, Номер 24(1)

Опубликована: Июль 27, 2024

Abstract The lung is a highly mechanical organ as it exposed to approximately 10 9 strain cycles, (where the length change of tissue structure per unit initial length), with an 4% amplitude during quiet tidal breathing or 7 cycles at 25% heavy exercises, sighs, and deep inspirations. These indices have been reported become aberrant in diseases such acute respiratory distress syndrome (ARDS), pulmonary hypertension, bronchopulmonary dysplasia (BPD), idiopathic fibrosis (IPF), asthma. Through recent innovations, various vitro systems/bioreactors used mimic lung’s developed. Among these, Flexcell tension system which composed bioreactors that utilize variety programs apply static cyclic on different cell-types established 2D monolayer cultures cell-embedded 3D hydrogel models, has enabled assessment response cells fibroblasts health disease. Fibroblasts are main effector responsible for production extracellular matrix (ECM) proteins repair maintain homeostasis implicated excessive deposition leads fibrosis. In this review, we summarise, studies bioreactor assess effects structure, function, phenotype homeostatic conditions abnormal environments associated injury We show these revealed regulate fibroblast proliferation, ECM protein production, inflammation normal diseased lung.

Язык: Английский

Highlights on Future Treatments of IPF: Clues and Pitfalls DOI Open Access

Alessandro Libra,

Enrico Sciacca,

Giuseppe Muscato

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(15), С. 8392 - 8392

Опубликована: Авг. 1, 2024

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by irreversible scarring of tissue, leading to death. Despite recent advancements in understanding its pathophysiology, IPF remains elusive, and therapeutic options are limited non-curative. This review aims synthesize the latest research developments, focusing on molecular mechanisms driving related emerging treatments. Unfortunately, several phase 2 studies showing promising preliminary results did not meet primary endpoints subsequent 3, underlying complexity need for new integrated endpoints. a challenging condition with complex interplay genetic, epigenetic, pathophysiological factors. Ongoing into keystones critical development targeted therapies that could potentially stop progression disease. Future directions include personalized medicine approaches, artificial intelligence integration, growth genetic insights, novel drug targets.

Язык: Английский

Процитировано

9
In vitro co-culture studies and the crucial role of fibroblast-immune cell crosstalk in IPF pathogenesis DOI Creative Commons

Fama Thiam,

Sakshi Phogat,

Filsan Ahmed Abokor

и другие.

Respiratory Research, Год журнала: 2023, Номер 24(1)

Опубликована: Ноя. 27, 2023

Язык: Английский

Процитировано

8
Loss of PTPN21 disrupted mitochondrial metabolic homeostasis and aggravated experimental pulmonary fibrosis DOI Creative Commons

Hui Lian,

Kai Xu, Ashley Chang

и другие.

Respiratory Research, Год журнала: 2024, Номер 25(1)

Опубликована: Дек. 4, 2024

Idiopathic pulmonary fibrosis (IPF) is a high-mortality lung disease with unclear pathogenesis. Convincing evidence suggests that an imbalance in mitochondrial homeostasis resulting from repeated injury to alveolar epithelial type 2 cells (AEC2) underlies IPF. Non-receptor protein tyrosine phosphatase 21 (PTPN21) performs various functions cancer; however, its role IPF has not been studied. This study aimed investigate the of PTPN21 fibrosis. The experimental results showed loss exacerbated by increasing cell numbers bronchoalveolar lavage fluid, hydroxyproline content, and extracellular matrix expression fibronectin α-smooth muscle actin (α-SMA) bleomycin-challenged mouse lungs. In A549 (AEC2), knockdown suppressed focal adhesion migration, reduced fission increased fusion, level superoxide, decreased membrane potential ATP levels. Simultaneously, impaired autophagy, intracellular reactive oxygen species Treatment fibroblasts (MRC-5) primary human (PHLF)) supernatant PTPN21-knockdown fibronectin, collagen 1 α-SMA. Conversely, overexpression produced opposite effects. However, treatment MRC-5 PHLF PTPN21-overexpressing only slightly cells, but did change summary, this revealed disrupted metabolic homeostasis, leading inactivation deposition proteins fibroblasts, thereby exacerbating

Язык: Английский

Процитировано

1
The effect of the mechanodynamic lung environment on fibroblast phenotype via the Flexcell DOI Creative Commons

S. Al Yazeedi,

A. F Abokor,

J. Brussow

и другие.

BMC Pulmonary Medicine, Год журнала: 2024, Номер 24(1)

Опубликована: Июль 27, 2024

Abstract The lung is a highly mechanical organ as it exposed to approximately 10 9 strain cycles, (where the length change of tissue structure per unit initial length), with an 4% amplitude during quiet tidal breathing or 7 cycles at 25% heavy exercises, sighs, and deep inspirations. These indices have been reported become aberrant in diseases such acute respiratory distress syndrome (ARDS), pulmonary hypertension, bronchopulmonary dysplasia (BPD), idiopathic fibrosis (IPF), asthma. Through recent innovations, various vitro systems/bioreactors used mimic lung’s developed. Among these, Flexcell tension system which composed bioreactors that utilize variety programs apply static cyclic on different cell-types established 2D monolayer cultures cell-embedded 3D hydrogel models, has enabled assessment response cells fibroblasts health disease. Fibroblasts are main effector responsible for production extracellular matrix (ECM) proteins repair maintain homeostasis implicated excessive deposition leads fibrosis. In this review, we summarise, studies bioreactor assess effects structure, function, phenotype homeostatic conditions abnormal environments associated injury We show these revealed regulate fibroblast proliferation, ECM protein production, inflammation normal diseased lung.

Язык: Английский

Процитировано

0