Related Experiment Video
Updated: May 16, 2026
10:12
Measuring Endoplasmic Reticulum Stress and Unfolded Protein Response in HIV-1 Infected T-Cells and Analyzing its Role in HIV-1 Replication
Published on: June 14, 2024
Endoplasmic reticulum stress as a pro-fibrotic stimulus
Harikrishna Tanjore1, William E Lawson, Timothy S Blackwell
1Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
Biochimica Et Biophysica Acta
|December 4, 2012
Summary
Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are key drivers of fibrosis in organs like the lungs and liver. Targeting ER stress may offer new therapeutic strategies for fibrotic diseases.
Area of Science:
- Cellular Biology
- Pathology
- Physiology
Background:
- Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) activation are implicated in fibrotic conditions across multiple organs.
- ER stress increases cellular susceptibility to pro-fibrotic stimuli, particularly in epithelial cells.
Purpose of the Study:
- To review the role of ER stress and UPR in fibrotic remodeling.
- To explore mechanisms linking ER stress to fibrosis and potential therapeutic targets.
Main Methods:
- Literature review of current evidence on ER stress and fibrosis.
- Analysis of pathways involved in ER stress-induced fibrotic remodeling.
Main Results:
- ER stress promotes fibrosis via apoptosis, epithelial-mesenchymal transition, and inflammation.
- Factors like metabolic issues, oxidative stress, viruses, and environmental exposures induce ER stress.
- Aging exacerbates ER stress, correlating with increased fibrosis incidence.
Conclusions:
- ER stress and UPR are critical determinants of fibrotic remodeling in various tissue fibrosis types.
- Further research is needed to elucidate ER stress mechanisms in fibrosis progression.
- Therapeutic targeting of ER stress and UPR warrants investigation for treating fibrotic diseases.
Related Concept Videos
01:17Role of ER in the Secretory Pathway
Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
01:31Regulation of the Unfolded Protein Response
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
01:37The Unfolded Protein Response
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
01:13Cell-matrix's Response to Mechanical Forces
In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue.
Anchoring junctions mechanically attach a cell to the...
Anchoring junctions mechanically attach a cell to the...
01:29Heart Failure II: Pathophysiology
Systolic Heart Failure and Compensatory MechanismsSystolic heart failure (also termed HFrEF, Heart Failure with Reduced Ejection Fraction) is the most prevalent type of heart filure. It results in a decreased volume of blood being pumped from the ventricle. The aortic arch and carotid sinuses have baroreceptors that detect reduced blood pressure, triggering the sympathetic nervous system (SNS) to release epinephrine and norepinephrine. Initially, this response aims to boost heart rate and...
01:26Protein Modifications in the RER
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.