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TRPM7 channels mediate the functional changes in cardiac fibroblasts induced by angiotensin II
Sha Li1, Mingjiang Li1, Xin Yi1
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Abstract:
Transient receptor potential melastatin 7 (TRPM7), a bifunctional channel protein owning both cation permeability and kinase activity, plays an important role in the pathophysiological process of many cell types, such as vascular smooth muscle cells, human glioma cells and mouse cortical astrocytes. However, whether TRPM7 channels play a key role in the functional change of cardiac fibroblasts (CFs) induced by angiotensin II (Ang II) remains unknown. Using Cell Counting Kit-8 (CCK-8) assay, immunofluorescence assay, western blot analysis, RT-qPCR, RNA interference (RNAi) and whole-cell patch-clamp techniques, the present study aimed to explore the role of TRPM7 channels in the proliferation, differentiation and collagen synthesis of CFs induced by Ang II. Our data showed that Ang II time-dependently increased TRPM7 expression and TRPM7 currents in the CFs. Downregulation of TRPM7 attenuated the TRPM7 current density, and inhibited the proliferation, differentiation and collagen synthesis of CFs induced by Ang II. Our results identified the TRPM7 channel as a pivotal member associated with the functional change of CFs induced by Ang II, and suggest that the TRPM7 channel may represent a promising therapeutic strategy for the treatment of fibrosis-related cardiac diseases.
Insights
Transient receptor potential melastatin 7 (TRPM7) channels are involved in cardiac fibroblast changes induced by angiotensin II. Inhibiting TRPM7 reduces proliferation and collagen synthesis, suggesting a therapeutic target for heart disease.
Area of Science:
- Cardiovascular Biology
- Ion Channel Physiology
- Cellular Signaling
Background:
- Transient receptor potential melastatin 7 (TRPM7) is a bifunctional protein with cation channel and kinase activity.
- TRPM7 is implicated in the pathophysiology of various cell types.
- The role of TRPM7 in angiotensin II-induced cardiac fibroblast (CF) function is not well understood.
Purpose of the Study:
- To investigate the role of TRPM7 channels in angiotensin II-induced proliferation, differentiation, and collagen synthesis in CFs.
- To determine if TRPM7 is a potential therapeutic target for fibrosis-related cardiac diseases.
Main Methods:
- Cell Counting Kit-8 (CCK-8) assay for proliferation.
- Immunofluorescence assay for differentiation.
- Western blot and RT-qPCR for gene and protein expression.
- RNA interference (RNAi) for TRPM7 downregulation.
- Whole-cell patch-clamp for TRPM7 currents.
Main Results:
- Angiotensin II increased TRPM7 expression and currents in CFs in a time-dependent manner.
- TRPM7 downregulation reduced TRPM7 current density.
- Inhibition of TRPM7 attenuated angiotensin II-induced CF proliferation, differentiation, and collagen synthesis.
Conclusions:
- TRPM7 channels are pivotal in angiotensin II-induced functional changes in CFs.
- TRPM7 represents a potential therapeutic target for treating fibrosis-related cardiac diseases.