Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Chemically induced expansion of type 2 alveolar epithelial cell promotes regenerative lower airway repair

ABSTRACT: To evaluate the effect of DPP4 inhibitor on regenerative repair of the lung upon injury, we carried out a single cell RNA sequencing study. In this study, orally administered sitagliptin was tested in LPS-induced lung injury model, followed by longitudinal single cell transcriptomic analysis with lung cells harvested at indicated time points.

ORGANISM(S): Mus musculus

PROVIDER: GSE262393 | GEO | 2024/03/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Chemically induced expansion of type 2 alveolar epithelial cell promotes regenerative lower airway repair [RNA-seq]

Project description:Type 2 alveolar epithelial cells (AEC2s) are stem cells in the adult lung that contribute to lower airway repair. Agents that promote the selective expansion of these cells might stimulate regeneration of the compromised alveolar epithelium, an etiology defining event in several pulmonary diseases. From a high content imaging screen of the drug repurposing library ReFRAME, we identified that dipeptidyl peptidase 4 (DPP4) inhibitors, widely used type 2 diabetes medications, selectively expand AEC2s and are broadly efficacious in several mouse models of lung damage. Mechanism of action studies revealed that the protease DPP4, in addition to processing incretin hormones, degrades IGF-1 and IL-6, essential regulators of AEC2 expansion whose levels are increased in the luminal compartment of the lung in response to drug treatment. To selectively target DPP4 in the lung with sufficient drug exposure, we developed NZ-97, a locally delivered, lung persistent DPP4 inhibitor that broadly promotes efficacy in mouse lung damage models with minimal peripheral exposure and good tolerability. This work reveals DPP4 as a central regulator of AEC2 expansion and affords a promising therapeutic approach to broadly stimulate regenerative repair in pulmonary disease.

2024-03-27 | GSE262398 | GEO

Chemically induced expansion of type 2 alveolar epithelial cell promotes regenerative lower airway repair

Project description:Chemically induced expansion of type 2 alveolar epithelial cell promotes regenerative lower airway repair

| PRJNA1091645 | ENA

Repurposing DPP4-Inhibition to Improve Hair Follicle Activation and Regeneration

Project description:Skin-injury and several diseases elicit fibrosis and induce hair follicle (HF)-growth arrest and loss. Resulting alopecia and disfiguration represent a severe burden for patients both physically and psychologically. Reduction of pro-fibrotic factors such as DPP4 might be a strategy to tackle this issue. We demonstrate DPP4-overrepresentation in settings with HF-growth arrest (telogen), HF-loss and non-regenerative wound areas in mice skin and human scalp. Topical DPP4-inhibition (DPP4i) with FDA/EMA-approved Sitagliptin (Sit) on preclinical models of murine HF-activation/regeneration results in accelerated anagen-progress, while treatment of wounds with Sit results in reduced expression of fibrosis markers, increased induction of anagen around wounds, and HF-regeneration in the wound center. These effects are associated with higher expression of Wnt-target Lef1, known to be required for HF-anagen (HF-activation)/regeneration. Sit-treatment decreases pro-fibrotic signaling in the skin, induce a differentiation trajectory of HF-cells, and activate Wnt-targets related to HF-activation/growth but not those supporting fibrosis. Taken together, our study demonstrates a role for DPP4 in HF biology and shows how DPP4i, currently used as oral medication to treat diabetes, could be repurposed into a topical treatment agent to potentially reverse HF-loss in alopecia and after injury.

2023-05-02 | GSE230514 | GEO

Chemically induced expansion of type 2 alveolar epithelial cell promotes regenerative lower airway repair [RNA-seq]

Project description:Chemically induced expansion of type 2 alveolar epithelial cell promotes regenerative lower airway repair [RNA-seq]

| PRJNA1091643 | ENA

Generation and expansion of induced respiratory airway progenitors (iRAPs) from human pluripotent stem cells.

Project description:Several novel distal lung populations were recently identified that may be involved in regeneration after injury.1–3 As these are absent in rodents, a deeper understanding of their roles and lineage relations requires availability of equivalent cells in vitro. Here we report the generation of expandable, clonal spheres, called induced respiratory airway progenitors (iRAPs), from human pluripotent stem cells. iRAPs consist mainly of previously identified type 0 alveolar epithelial (AT0) cells, terminal respiratory bronchiole stem cells (TRB-SCs) and distal basal cells (BCs).3 Velocity analysis of single cell RNAseq data suggests that distal BCs are the most undifferentiated progenitors in the iRAPs and give rise to AT0 cells. iRAPs will be an important resource for studies in human lung regeneration, and potentially for regenerative approaches for human lung disease.

2025-01-13 | GSE225301 | GEO

Transcriptome Analysis of Fibroblasts in Hypoxia-Induced Vascular Remodeling: Functional Roles of CD26/DPP4

Project description:In hypoxic pulmonary hypertension (PH), pulmonary vascular remodeling is characterized by the emergence of activated adventitial fibroblasts, leading to medial smooth muscle hyperplasia. Previous studies have suggested that CD26/dipeptidyl peptidase-4 (DPP4) plays a crucial role in the pathobiological processes in lung diseases. However, its role in pulmonary fibroblasts in hy-poxic PH remains unknown. Therefore, we aimed to clarify the mechanistic role of CD26/DPP4 in lung fibroblasts in hypoxic PH. Dpp4 knockout (Dpp4 KO) and wild-type (WT) mice were exposed to hypoxia for 4 weeks. The degree of PH severity and medial wall thickness was augmented in Dpp4 KO mice compared with that in WT mice, suggesting that CD26/DPP4 plays a suppressive role in the development of hypoxic PH. Transcriptome analysis of human lung fibroblasts cultured under hypoxic conditions revealed that TGFB2, TGFB3, and TGFA were all upregulated as differentially expressed genes after DPP4 knockdown with small interfering RNA treatment. These results suggest that CD26/DPP4 plays a suppressive role in TGFβ signal-regulated fibroblast ac-tivation under hypoxic conditions. Therefore, CD26/DPP4 may be a potential therapeutic target in patients with PH associated with chronic hypoxia.

2024-11-17 | GSE281533 | GEO

Angiotensin receptor blockade attenuates cigarette smoke-induced lung injury and rescues lung architecture in a murine model

Project description:TGFβ inhibition attenuates chronic cigarette smoke induced lung injury and rescues lung architecture. AKR/J mice were exposed to Cigarette Smoke (CS) for a period of two months. Some animals received a treatment of Losartan (.6gr/L) orally while exposed (CS Los). These two groups are to be compared to animals that remained in Room Air (RA) and Room Air plus Losartan(0.6g/L) (RA Los) for any changes.

2011-12-30 | E-GEOD-33561 | biostudies-arrayexpress

Lower Airway Microbiota.

Project description:During the last several years, the interest in the role of microbiota in human health has grown significantly. For many years, the lung was considered a sterile environment, and only recently, with the use of more sophisticated techniques, has it been demonstrated that colonization by a complex population of microorganisms in lower airways also occurs in healthy subjects; a predominance of some species of Proteobacteria, Firmicutes, and Bacteroidetes phyla and with a peculiar composition in some disease conditions, such as asthma, have been noted. Lung microbiota derives mainly from the higher airways microbiota. Although we have some information about the role of gut microbiota in modulation of immune system, less it is known about the connection between lung microbiota and local and systemic immunity. There is a correlation between altered microbiota composition and some diseases or chronic states; however, despite this correlation, it has not been clearly demonstrated whether the lung microbiota dysbiosis could be a consequence or a cause of these diseases. We are far from a scientific approach to the therapeutic use of probiotics in airway diseases, but we are only at the starting point of a knowledge process in this fascinating field that could reveal important surprises, and randomized prospective studies in future could reveal more about the clinical possibilities for controlling lung microbiota. This review was aimed at updating the current knowledge in the field of airway microbiota.

| S-EPMC6776601 | biostudies-literature

Airway-Associated Macrophages in Homeostasis and Repair

Project description:We isolated CD45+ cells after injury (Uninjured, Day1, Day4 and Day7) and CD45+F4/80+ cells from tracheal mesenchyme and dissociated lung, as well as CD45+ cells from peeled tracheal epithelium.

2020-12-30 | GSE152501 | GEO

Influenza B virus infection alters regenerative potential of alveolar type 2 pneumocytes (RNA-Seq)

Project description:Alveolar type 2 cells proliferate after lung injury. It was found that survivor alveolar type 2 cells downregulate genes relating to developmental, proliferation and differentiation pathways.

2025-01-06 | GSE275874 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data