Related Experiment Video
Updated: Jan 27, 2026
Isolation of Human Myoblasts, Assessment of Myogenic Differentiation, and Store-operated Calcium Entry Measurement
Published on: July 26, 2017
A potential new approach for treating systemic sclerosis: Dedifferentiation of SSc fibroblasts and change in the
Ching-Ying Wu1,2,3, Wen-Li Hsu2,4, Ming-Hsien Tsai5
1Department of Dermatology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Abstract:
Transforming growth factor-β (TGF-β) is an important target for treating systemic sclerosis (SSc). However, our study revealed three levels of TGF-β1 expression in SSc patients, indicating that inhibiting TGF-β is not sufficient to treat SSc. A previous clinical trial also displayed disappointing results. Thus, our study attempted to search for a potential novel approach. Ingenuity Pathway Analysis (IPA) indicated that the SSc pathological pathways were closely associated with store-operated Ca2+ entry (SOCE)-regulated signals, and SOCE activity was found to be increased in SSc fibroblasts. Further treatment of SSc fibroblasts with SOCE inhibitors, 2APB, and associated calcium channel inhibitors SKF96365, and indomethacin, showed that the SOCE inhibitors selectively decreased fibrosis markers and altered the cell morphology. Consequently, SOCE inhibitors, especially 2APB and indomethacin, caused the dedifferentiation of SSc fibroblasts via cytoskeleton remodeling and altered collagen secretion and restored the cell mobility. We further explained SSc pathogenesis as fibroblast differentiation with SOCE. Treatment with exogenous factors, gelatin-1, FAM20A and human albumin, which were identified from the conditioned medium of SSc fibroblasts, was important for regulating the differentiation of fibroblasts with higher levels of SOCE and α-SMA. Conclusively, to treat SSc, blockage of the increased SOCE activity in SSc induces the dedifferentiation of SSc fibroblasts and simultaneously changes the extracellular matrix (ECM) structure to limit SSc pathogenesis.
Insights
Systemic sclerosis (SSc) treatment requires targeting store-operated calcium entry (SOCE). Inhibiting SOCE in SSc fibroblasts reduces fibrosis and promotes dedifferentiation, offering a novel therapeutic strategy for SSc.
Area of Science:
- Cell Biology
- Biochemistry
- Immunology
Background:
- Transforming growth factor-β (TGF-β) is a key target for systemic sclerosis (SSc), but its inhibition alone is insufficient.
- Previous clinical trials targeting TGF-β for SSc have yielded disappointing results.
- This study explores novel therapeutic targets for SSc beyond TGF-β.
Purpose of the Study:
- To investigate the role of store-operated calcium entry (SOCE) in SSc pathogenesis.
- To evaluate the therapeutic potential of SOCE inhibitors in SSc fibroblasts.
- To elucidate the mechanism by which SOCE influences fibroblast differentiation and extracellular matrix (ECM) remodeling in SSc.
Main Methods:
- Ingenuity Pathway Analysis (IPA) to identify SSc-associated pathways.
- Assessing SOCE activity in SSc fibroblasts.
- Treating SSc fibroblasts with SOCE inhibitors (2APB, SKF96365, indomethacin).
- Analyzing fibrosis markers, cell morphology, cytoskeleton remodeling, collagen secretion, and cell mobility.
Main Results:
- IPA revealed a strong association between SSc pathology and SOCE-regulated signals.
- SOCE activity was significantly increased in SSc fibroblasts.
- SOCE inhibitors selectively reduced fibrosis markers, altered cell morphology, and induced fibroblast dedifferentiation.
- Inhibitors also modulated collagen secretion and restored cell mobility, suggesting a role for SOCE in fibroblast differentiation.
Conclusions:
- Increased SOCE activity in SSc fibroblasts drives disease pathogenesis.
- Blocking SOCE in SSc fibroblasts promotes dedifferentiation and alters ECM structure.
- SOCE inhibitors represent a promising novel therapeutic strategy for systemic sclerosis.
Related Concept Videos
01:12Energy Stored in a Capacitor
01:10Energy Stored in Capacitors
By integrating the equation that relates voltage and current in a capacitor, one can derive an equation for the voltage across the capacitor at any given time. This equation is crucial in understanding and predicting the behavior of capacitors in...
01:16Energy Stored in Inductors
In terms of gauging the energy stored within an inductor, it is equivalent to the integral of the power delivered at every individual moment, all...
01:26Energy Stored in a Capacitor: Problem Solving
Capacitor-discharge ignition is a type of ignition system commonly found in small engines where the energy released from a capacitor ignites an induction coil that, in turn, fires the spark plug.
To calculate the energy stored in a capacitor of...
01:31Energy Stored In A Coaxial Cable
In the simplest form, a coaxial cable can be represented by two long hollow concentric cylinders in which the current flows in opposite directions. The magnetic field inside and outside the coaxial cable is determined by using Ampère's law. The magnetic field inside...
03:02Standard Electrode Potentials