Page last updated: 2024-10-24

bronchiole development

Definition

Target type: biologicalprocess

The biological process whose specific outcome is the progression of a bronchiole from an initial condition to its mature state. This process begins with the formation of the bronchiole and ends with the mature structure. A bronchiole is the first airway branch that no longer contains cartilage; it is a branch of the bronchi. [GOC:dph, GOC:mtg_lung]

Bronchiole development is a complex process that begins during fetal life and continues into early childhood. It involves the branching of the trachea into smaller and smaller airways, ultimately forming the bronchioles, which are the smallest airways in the lungs. This process is crucial for the development of a functional respiratory system, enabling gas exchange between the air and the bloodstream.

The process of bronchiole development can be broken down into several key steps:

1. **Epithelial Budding:** During early fetal development, the trachea begins to form as a hollow tube lined by epithelial cells. At around the 6th week of gestation, epithelial cells at the tip of the trachea start to proliferate and bud outwards, initiating the branching process.

2. **Branching Morphogenesis:** The epithelial buds continue to elongate and branch, forming a network of interconnected airways. This branching process is driven by complex interactions between epithelial cells and the surrounding mesenchyme, which provides structural support and signaling molecules.

3. **Epithelial Differentiation:** As the bronchioles develop, the epithelial lining undergoes differentiation, leading to the formation of specialized cell types. These include ciliated cells, which help to move mucus and debris out of the airways, goblet cells, which produce mucus to trap foreign particles, and club cells, which have a protective function.

4. **Smooth Muscle Development:** Smooth muscle cells develop around the bronchioles, providing contractile force that helps to regulate airflow. This process is also influenced by interactions between the epithelial cells and the surrounding mesenchyme.

5. **Blood Vessel Formation:** As the bronchioles develop, blood vessels are formed in the surrounding mesenchyme, providing oxygen and nutrients to the developing airways.

6. **Postnatal Development:** Bronchiole development continues after birth, with further branching and specialization of the epithelial lining. This process is influenced by factors such as exposure to air and the development of the immune system.

7. **Regulation of Bronchiole Development:** Several factors are known to regulate bronchiole development, including:

- **Growth Factors:** Factors such as fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF)-beta play crucial roles in branching morphogenesis and epithelial differentiation.

- **Transcription Factors:** Transcription factors like SHH and GATA6 regulate the expression of genes involved in bronchiole development.

- **Extracellular Matrix:** The extracellular matrix, which surrounds the developing airways, provides structural support and signals that influence branching and epithelial differentiation.

- **Mechanical Forces:** Mechanical forces, such as fluid flow and stretch, can also influence bronchiole development.

8. **Clinical Relevance:** Disruptions in bronchiole development can lead to a variety of respiratory problems, including bronchopulmonary dysplasia (BPD), a common lung disease in premature infants, and asthma. Understanding the complex mechanisms that regulate bronchiole development is essential for developing new therapies for these conditions.'
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Proteins (2)

ProteinDefinitionTaxonomy
Macrophage metalloelastaseA macrophage metalloelastase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P39900]Homo sapiens (human)
Integrin beta-6An integrin beta-6 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P18564]Homo sapiens (human)

Compounds (17)

CompoundDefinitionClassesRoles
5-phenylhydantoin, (+-)-isomer5-phenylhydantoin: structure given in first source
clodronic acidclodronic acid : An organochlorine compound that is methylene chloride in which both hydrogens are replaced by phosphonic acid groups. It inhibits bone resorption and soft tissue calcification, and is used (often as the disodium salt tetrahydrate) as an adjunct in the treatment of severe hypercalcaemia associated with malignancy, and in the management of osteolytic lesions and bone pain associated with skeletal metastases.

Clodronic Acid: A diphosphonate which affects calcium metabolism. It inhibits bone resorption and soft tissue calcification.
1,1-bis(phosphonic acid);
one-carbon compound;
organochlorine compound
antineoplastic agent;
bone density conservation agent
marimastatmarimastat : A secondary carboxamide resulting from the foraml condensation of the carboxy group of (2R)-2-[(1S)-1-hydroxy-2-(hydroxyamino)-2-oxoethyl]-4-methylpentanoic acid with the alpha-amino group of N,3-dimethyl-L-valinamide.

marimastat: a matrix metalloproteinase inhibitor active in patients with advanced carcinoma of the pancreas, prostate, or ovary
hydroxamic acid;
secondary carboxamide
antineoplastic agent;
matrix metalloproteinase inhibitor
ilomastatCS 610: matrix metalloproteinase inhibitor; structure in first source

ilomastat : An N-acyl-amino acid obtained by formal condensation of the carboxy group of (2R)-2-[2-(hydroxyamino)-2-oxoethyl]-4-methylpentanoic acid with the amino group of N-methyl-L-tryptophanamide. A cell permeable broad-spectrum matrix metalloproteinase (MMP) inhibitor
hydroxamic acid;
L-tryptophan derivative;
N-acyl-amino acid
anti-inflammatory agent;
antibacterial agent;
antineoplastic agent;
EC 3.4.24.24 (gelatinase A) inhibitor;
neuroprotective agent
cilengitideCilengitide: an alphaVbeta3 integrin antagonist that paralyzes cancer cellsoligopeptide
taxifolin(+)-taxifolin : A taxifolin that has (2R,3R)-configuration.taxifolinmetabolite
quercetin7-hydroxyflavonol;
pentahydroxyflavone
antibacterial agent;
antineoplastic agent;
antioxidant;
Aurora kinase inhibitor;
chelator;
EC 1.10.99.2 [ribosyldihydronicotinamide dehydrogenase (quinone)] inhibitor;
geroprotector;
phytoestrogen;
plant metabolite;
protein kinase inhibitor;
radical scavenger
luteolin3'-hydroxyflavonoid;
tetrahydroxyflavone
angiogenesis inhibitor;
anti-inflammatory agent;
antineoplastic agent;
apoptosis inducer;
c-Jun N-terminal kinase inhibitor;
EC 2.3.1.85 (fatty acid synthase) inhibitor;
immunomodulator;
nephroprotective agent;
plant metabolite;
radical scavenger;
vascular endothelial growth factor receptor antagonist
isoacteosideisoacteoside: a phenylethanoid glycoside isolated from Indian paintbrush (Verbenaceae) Castilleja linariaefolia; also in other plants; structure given in first sourcehydroxycinnamic acid
Methyl rosmarinatehydroxycinnamic acid
(11c)cgs 25966
cyclic(arg-gly-asp-d-phe-val)
ageladine aageladine A : An imidazopyridine that is 1H-imidazo[4,5-c]pyridin-2-amine substituted by a 4,5-dibromo-1H-pyrrol-2-yl group at position 4. It is an alkaloid isolated from a marine sponge Agelas nakamurai and acts as an inhibitor of the matrix metalloproteinases, the key enzymes involved in tumour growth, migration, angiogenesis, invasion and metastasis.

Ageladine A: an antiangiogenic matrixmetalloproteinase inhibitor from the marine sponge Agelas nakamurai; structure in first source
alkaloid;
aromatic amine;
imidazopyridine;
organobromine compound;
pyrroles
angiogenesis inhibitor;
antineoplastic agent;
matrix metalloproteinase inhibitor;
metabolite
N(2)-([biphenyl]-4-ylsulfonyl)-N-hydroxy-N(2)-isopropoxy-D-valinamideN(2)-([biphenyl]-4-ylsulfonyl)-N-hydroxy-N(2)-isopropoxy-D-valinamide : A hydroxamic acid that is N-hydroxy-D-valinamide in which the alpha-amino group has been substituted by isopropoxy and [biphenyl]-4-ylsulfonyl groups. A selective matrix metalloproteinase-2 (MMP-2) inhibitor, it is one of the most potent inducers of autophagy. Its physiological roles include angiogenesis, cancer metastasis, embryogenesis, tissue remodeling in development, and wound healing.D-valine derivative;
hydroxamic acid
antineoplastic agent;
autophagy inducer;
EC 3.4.24.24 (gelatinase A) inhibitor;
melanin synthesis inhibitor
bms-566394BMS-566394: structure in first source
incb3619INCB3619: ADAM inhibitor; structure in first source
grassystatin agrassystatin A: isolated from a cyanobacterium, identified as Lyngbya cf.; structure in first source