scholarly journals Acquisition of cellular properties during alveolar formation requires differential activity and distribution of mitochondria

2021 ◽  
Author(s):  
Kuan Zhang ◽  
Erica Yao ◽  
Julia Wong ◽  
Paul J. Wolters ◽  
Pao-Tien Chuang
Keyword(s):  
Epithelial Cells ◽  
Mitochondrial Function ◽  
Shape Change ◽  
Alveolar Epithelial Cells ◽  
Mitochondrial Activity ◽  
Cellular Functions ◽  
Alveolar Epithelial ◽  
Cell Shape Change ◽  
And Migration ◽  
Alveolar Formation

AbstractAlveolar formation requires coordinated movement and interaction between alveolar epithelial cells, mesenchymal myofibroblasts and endothelial cells/pericytes to produce secondary septa. These processes rely on the acquisition of distinct cellular properties to enable ligand secretion for cell-cell signaling and initiate morphogenesis through cell migration and cell shape change. In this study, we showed that mitochondrial activity and distribution play a key role in bestowing cellular functions on both alveolar epithelial cells and mesenchymal myofibroblasts for generating secondary septa to form alveoli. These results suggest that mitochondrial function is tightly regulated to empower cellular machineries in a spatially specific manner. Indeed, such regulation via mitochondria is required for secretion of platelet-derived growth factor from alveolar epithelial cells to influence myofibroblast proliferation and migration. Moreover, mitochondrial function enables myofibroblast migration during alveolar formation. Together, these findings yield novel mechanistic insights into how mitochondria regulate pivotal steps of alveologenesis. They highlight selective utilization of energy and diverse energy demands in different cellular processes during development. Our work serves as a paradigm for studying how mitochondria control tissue patterning.

scholarly journals A mammalian Wnt5a–Ror2–Vangl2 axis controls the cytoskeleton and confers cellular properties required for alveologenesis

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Kuan Zhang ◽  
Erica Yao ◽  
Chuwen Lin ◽  
Yu-Ting Chou ◽  
Julia Wong ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Planar Cell Polarity ◽  
Current Model ◽  
Alveolar Epithelial Cells ◽  
Alveolar Type ◽  
Type I ◽  
Alveolar Epithelial ◽  
Pcp Signaling ◽  
And Migration ◽  
Alveolar Formation

Alveolar formation increases the surface area for gas-exchange and is key to the physiological function of the lung. Alveolar epithelial cells, myofibroblasts and endothelial cells undergo coordinated morphogenesis to generate epithelial folds (secondary septa) to form alveoli. A mechanistic understanding of alveologenesis remains incomplete. We found that the planar cell polarity (PCP) pathway is required in alveolar epithelial cells and myofibroblasts for alveologenesis in mammals. Our studies uncovered a Wnt5a–Ror2–Vangl2 cascade that endows cellular properties and novel mechanisms of alveologenesis. This includes PDGF secretion from alveolar type I and type II cells, cell shape changes of type I cells and migration of myofibroblasts. All these cellular properties are conferred by changes in the cytoskeleton and represent a new facet of PCP function. These results extend our current model of PCP signaling from polarizing a field of epithelial cells to conferring new properties at subcellular levels to regulate collective cell behavior.

Resolvin E1 Improves Mitochondrial Function in Human Alveolar Epithelial Cells during Severe Inflammation

Lipids ◽  
2019 ◽  
Vol 54 (1) ◽  
pp. 53-65 ◽  
Author(s):  
Konstantin Mayer ◽  
Natascha Sommer ◽  
Karl Hache ◽  
Andreas Hecker ◽  
Sylvia Reiche ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mitochondrial Function ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial ◽  
Severe Inflammation ◽  
Human Alveolar Epithelial Cells

scholarly journals β-Catenin/T-cell Factor Signaling Is Activated during Lung Injury and Promotes the Survival and Migration of Alveolar Epithelial Cells

2009 ◽  
Vol 285 (5) ◽  
pp. 3157-3167 ◽  
Author(s):  
Annette S. Flozak ◽  
Anna P. Lam ◽  
Susan Russell ◽  
Manu Jain ◽  
Ofra N. Peled ◽  
...  
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
Lung Injury ◽  
Alveolar Epithelial Cells ◽  
T Cell Factor ◽  
Alveolar Epithelial ◽  
And Migration

Sodium tanshinone IIA sulfonate attenuates cigarette smoke extract-induced mitochondrial dysfunction, oxidative stress and apoptosis in alveolar epithelial cells by enhancing SIRT1 pathway

2021 ◽  
Author(s):  
Ruijuan Guan ◽  
Hongwei Yao ◽  
Ziying Li ◽  
Jing Qian ◽  
Liang Yuan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Mitochondrial Dysfunction ◽  
Cigarette Smoke ◽  
Mitochondrial Function ◽  
A549 Cells ◽  
Alveolar Epithelial Cells ◽  
Tanshinone Iia ◽  
Alveolar Epithelial ◽  
Sodium Tanshinone Iia Sulfonate

Abstract Emphysema is one of the most important phenotypes for chronic obstructive pulmonary disease (COPD). Apoptosis in alveolar epithelial cells (AECs) causes the emphysematous alterations in the smokers and patients with COPD. Sirtuin 1 (SIRT1) is able to attenuate mitochondrial dysfunction, oxidative stress, and to modulate apoptosis. It has been shown that sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA, protects against cigarette smoke (CS)-induced emphysema/COPD in mice. However, the mechanisms underlying these findings remain unclear. Here, we investigate whether and how STS attenuates on AEC apoptosis via a SIRT1-dependent mechanism. We found that STS treatment decreased CS extract (CSE)-induced apoptosis in human alveolar epithelial A549 cells. STS reduced oxidative stress, improved mitochondrial function and mitochondrial membrane potential (ΔΨm), and restored mitochondrial dynamics-related protein expression. Moreover, STS promoted mitophagy, and increased oxidative phosphorylation (OXPHOS) protein levels (Complexes I-IV) in CSE-stimulated A549 cells. The protective effects of STS were associated with SIRT1 upregulation, since SIRT1 inhibition by EX 527 significantly attenuated or abolished the ability of STS to reverse the CSE-induced mitochondrial damage, oxidative stress, and apoptosis in A549 cells. In conclusion, STS ameliorates CSE-induced AEC apoptosis by improving mitochondrial function and reducing oxidative stress via enhancing SIRT1 pathway. These findings provide novel mechanisms underlying the protection of STS against CS-induced COPD.

scholarly journals Mesenchymal Stem Cell Conditioned Medium Promotes Proliferation and Migration of Alveolar Epithelial Cells under Septic Conditions In Vitro via the JNK-P38 Signaling Pathway

2015 ◽  
Vol 37 (5) ◽  
pp. 1830-1846 ◽  
Author(s):  
Jie Chen ◽  
Yanqin Li ◽  
Haojie Hao ◽  
Chonghui Li ◽  
Yu Du ◽  
...  
Keyword(s):  
Stem Cell ◽  
Botulinum Toxin ◽  
Epithelial Cells ◽  
Mesenchymal Stem Cell ◽  
Conditioned Medium ◽  
Alveolar Epithelial Cells ◽  
Receptor Type ◽  
Alveolar Epithelial ◽  
And Migration ◽  
Proliferation And Migration

Background/Aims: Mesenchymal stem cell (MSC) based therapies may be useful for treating acute respiratory distress syndrome (ARDS), but the underlying mechanisms are incompletely understood. We investigated the impact of human umbilical cord Wharton's jelly-derived MSC (hUC-MSC) secreted factors on alveolar epithelial cells under septic conditions and determined the relevant intracellular signaling pathways. Methods: Human alveolar epithelial cells (AEC) and primary human small airway epithelial cells (SAEC) were subjected to lipopolysaccharide (LPS) with or without the presence of hUC-MSC-conditioned medium (CM). Proliferation and migration of AEC and SAEC were determined via an MTT assay, a wound healing assay and a transwell migration assay (only for AEC). Protein phosphorylation was determined by western blot and the experiments were repeated in presence of small-molecule inhibitors. The hMSC-secretory proteins were identified by LC-MS/MS mass spectrometry. Results: MSC-CM enhanced proliferation and migration. Activation of JNK and P38, but not ERK, was required for the proliferation and migration of AEC and SAEC. Pretreatment of AEC or SAEC with SP600125, an inhibitor of JNK1 or SB200358, an inhibitor of P38, significantly reduced cell proliferation and migration. An array of proteins including TGF-beta receptor type-1, TGF-beta receptor type-2, Ras-related C3 botulinum toxin substrate 1 and Ras-related C3 botulinum toxin substrate 2 which influencing the proliferation and migration of AEC and SAEC were detected in MSC-CM. Conclusion: Our data suggest MSC promote epithelial cell repair through releasing a repertoire of paracrine factors via activation of JNK and P38 MAPK.

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