miR‐20a‐5p regulates pulmonary surfactant gene expression in alveolar type II cells

Gong, Yongjian; Xu, Weidong; Chen, Yang; Liu, Yun; Yang, Yuan; Wang, Beibei; Lu, Zhitao; Lin, Hung‐Chih; Zhou, Xiaoyu

doi:10.1111/jcmm.14639

Cited by 8 publications

(7 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, our analysis of the AFSC-EV miRNA cargo and downregulated genes revealed 28 miRNAs that play a role in restored epithelial and mesenchymal cell differentiation, as well as branching morphogenesis. As an example, miR-20-5p, which belongs to the miR17~92 family, is of particular interest as it controls pulmonary surfactant gene expression in AT2 cells [55]. In addition to this cluster, miR-28-5p was also found in our network to regulate Robo1 and Pdgfra , and has been reported to be decreased in the nitrofen model of CDH [7,56].…”

Section: Discussionmentioning

confidence: 97%

Amniotic fluid stem cell extracellular vesicles promote fetal lung branching and cell differentiation in experimental congenital diaphragmatic hernia

Khalaj

Figueira

Antounians

et al. 2022

Preprint

View full text Add to dashboard Cite

Pulmonary hypoplasia secondary to congenital diaphragmatic hernia (CDH) is characterized by impaired branching morphogenesis and differentiation. We have previously demonstrated that administration of extracellular vesicles derived from rat amniotic fluid stem cells (AFSC-EVs) rescues development of hypoplastic lungs at the pseudoglandular and alveolar stages in rodent models of CDH. Herein, we tested whether AFSC-EVs exert their regenerative effects at the canalicular and saccular stages, as these are translationally relevant for clinical intervention. To induce fetal pulmonary hypoplasia, we gavaged rat dams with nitrofen at embryonic day 9.5 and demonstrated that nitrofen-exposed lungs had impaired branching morphogenesis, dysregulated signaling pathways relevant to lung development (FGF10/FGFR2, ROBO/SLIT, Ephrin, Neuropilin 1, beta-catenin) and impaired epithelial and mesenchymal cell marker expression at both stages. AFSC-EVs administered to nitrofen-exposed lung explants rescued airspace density and increased the expression levels of key factors responsible for branching morphogenesis. Moreover, AFSC-EVs rescued the expression of alveolar type 1 and 2 cell markers at both canalicular and saccular stages, and restored markers of club, ciliated epithelial, and pulmonary neuroendocrine cells at the saccular stage. AFSC-EV treated lungs also had restored markers of lipofibroblasts and PDGFRA+ cells to control levels at both stages. EV tracking showed uptake of AFSC-EV RNA cargo throughout the fetal lung and an mRNA-miRNA network analysis identified that several miRNAs responsible for regulating lung development processes were contained in the AFSC-EV cargo. These findings suggest that AFSC-EV based therapies hold potential for restoring fetal lung growth and maturation in babies with pulmonary hypoplasia secondary to CDH.

show abstract

Section: Discussionmentioning

confidence: 97%

Amniotic fluid stem cell extracellular vesicles promote fetal lung branching and cell differentiation in experimental congenital diaphragmatic hernia

Khalaj

Figueira

Antounians

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…As an example, miR-20-5p, which belongs to the miR17~92 family, is of particular interest as it controls pulmonary surfactant gene expression in AT2 cells. 57 Through antagomir studies, we demonstrated that miR-20-5p is responsible for AFSC-EV rescue effect of impaired autophagy, a key cellular mechanism that is dysregulated in CDH lungs. 58 In addition to this cluster, miR-28-5p was also found in our network to regulate Robo1 and Pdgfra , and has been reported to be decreased in the nitrofen model of CDH.…”

Section: Discussionmentioning

confidence: 91%

Treatment with Amniotic Fluid Stem Cell Extracellular Vesicles Promotes Fetal Lung Branching and Cell Differentiation at Canalicular and Saccular Stages in Experimental Pulmonary Hypoplasia Secondary to Congenital Diaphragmatic Hernia

Khalaj

Figueira

Antounians

et al. 2022

Stem Cells Translational Medicine

View full text Add to dashboard Cite

Pulmonary hypoplasia secondary to congenital diaphragmatic hernia (CDH) is characterized by impaired branching morphogenesis and differentiation. We have previously demonstrated that administration of extracellular vesicles derived from rat amniotic fluid stem cells (AFSC-EVs) rescues development of hypoplastic lungs at the pseudoglandular and alveolar stages in rodent models of CDH. Herein, we tested whether AFSC-EVs exert their regenerative effects at the canalicular and saccular stages, as these are translationally relevant for clinical intervention. To induce fetal pulmonary hypoplasia, we gavaged rat dams with nitrofen at embryonic day 9.5 and demonstrated that nitrofen-exposed lungs had impaired branching morphogenesis, dysregulated signaling pathways relevant to lung development (FGF10/FGFR2, ROBO/SLIT, Ephrin, Neuropilin 1, β-catenin) and impaired epithelial and mesenchymal cell marker expression at both stages. AFSC-EVs administered to nitrofen-exposed lung explants rescued airspace density and increased the expression levels of key factors responsible for branching morphogenesis. Moreover, AFSC-EVs rescued the expression of alveolar type 1 and 2 cell markers at both canalicular and saccular stages and restored markers of club, ciliated epithelial, and pulmonary neuroendocrine cells at the saccular stage. AFSC-EV-treated lungs also had restored markers of lipofibroblasts and PDGFRA+ cells to control levels at both stages. EV tracking showed uptake of AFSC-EV RNA cargo throughout the fetal lung and an mRNA-miRNA network analysis identified that several miRNAs responsible for regulating lung development processes were contained in the AFSC-EV cargo. These findings suggest that AFSC-EV-based therapies hold potential for restoring fetal lung growth and maturation in babies with pulmonary hypoplasia secondary to CDH.

show abstract

“…For example, decreased miRNA biogenesis by silencing Drosha enhanced the potential of human alveolar type II cells to secrete SP-A protein [30]. Furthermore, several in vitro or in vivo studies revealed that miRNAs such as miR-200 family [31], miR-29 [32], miR-20a-5p [33], and miR-16 [34] positively regulate pulmonary surfactant proteins synthesis whereas miR-431-5p [30], miR-199a/214 cluster [36], miR-26a [37][38][39], miR-206 [40] were found to exert an inhibitory role in AECII differentiation and synthesis of surfactant proteins (Table 3). Interestingly, it has been also reported that SP-A2 (SP-A has two variants: SP-A1 and SP-A2) regulates miRNome of alveolar macrophages (AM) in a sex-specific manner.…”

Section: Mirna-clr Axes In Developmental and Physiological Homeostasismentioning

confidence: 99%

Interplay between C‐type lectin receptors and microRNAs in cellular homeostasis and immune response

2020

View full text Add to dashboard Cite

C-type lectin receptors (CLRs) belong to the family of pattern recognition receptors (PRRs). They have a critical role to play in the regulation of a range of physiological functions including development, respiration, angiogenesis, inflammation, and immunity. CLRs can recognize distinct and conserved exogenous pathogen-associated as well as endogenous damageassociated molecular patterns. These interactions set off downstream signaling cascades, leading to the production of inflammatory mediators, activation of effector immune cells as well as regulation of the developmental and physiological homeostasis. CLR signaling must be tightly controlled to circumvent the excessive inflammatory burden and to maintain the cellular homeostasis. Recently, MicroRNAs (miRNAs) have been shown to be important regulators of expression of CLRs and their downstream signaling. The delicate balance between miRNAs and CLRs seems crucial in almost all aspects of multicellular life. Any dysregulations in the miRNA-CLR axes may lead to tumorigenesis or inflammatory diseases. Here, we present an overview of the current understanding of the central role of miRNAs in the regulation of CLR expression, profoundly impacting upon homeostasis and immunity, and thus, development of therapeutics against immune disorders.

show abstract

miR‐20a‐5p regulates pulmonary surfactant gene expression in alveolar type II cells

Cited by 8 publications

References 36 publications

Amniotic fluid stem cell extracellular vesicles promote fetal lung branching and cell differentiation in experimental congenital diaphragmatic hernia

Amniotic fluid stem cell extracellular vesicles promote fetal lung branching and cell differentiation in experimental congenital diaphragmatic hernia

Treatment with Amniotic Fluid Stem Cell Extracellular Vesicles Promotes Fetal Lung Branching and Cell Differentiation at Canalicular and Saccular Stages in Experimental Pulmonary Hypoplasia Secondary to Congenital Diaphragmatic Hernia

Interplay between C‐type lectin receptors and microRNAs in cellular homeostasis and immune response

Contact Info

Product

Resources

About