In the past years, cardiac mortality has decreased, but cardiac diseases are still responsible for millions of deaths every year worldwide. Bone-marrow mesenchymal stem cells (BMSCs) transplantation may be a promising therapeutic strategy because of its capacity to differentiate into cardiac cells. Current research indicates that chemical substances, microRNAs, and cytokines have biological functions that regulate the cardiomyocytes differentiation of BMSCs. In this review, we chiefly summarize the regulatory factors that induce BMSCs to differentiate into cardiomyocytes.

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Cardiomyocyte differentiation of mesenchymal stem cells from bone marrow: new regulators and its implications.

The ubiquitous expression in many organs throughout the body and the ability to respond to a wide variety of physical and chemical stimuli have brought transient receptor potential (TRP) channels to the vanguards of our sensory systems. TRP vanilloid-1 (TRPV1) is the founding member of the TRPV subfamily. TRPV1 can be activated by noxious heat, protons, and vanilloids. Previous studies have shown that TRPV1 is located on the plasma membrane, serving to non-selectively permeate calcium ion from the extracellular region to the cytoplasm. Interestingly, increasing evidence suggests that TRPV1 is also located intracellularly in various cell types such as neurons, myocytes, and numerous cancer cells. By immunocytochemistry and/or fractionation followed by Western blotting, TRPV1 was found to express on the endoplasmic reticulum/sarcoplasmic reticulum and the mitochondria. By using various pharmacological and molecular tools, intracellular TRPV1 was also found to functionally express to control calcium level both inside the organelles and in the cytoplasm. Recent studies have shown that intracellularly located TRPV1 serves versatile functions in various physiological and pathological conditions (e.g., exercise endurance and hypertrophy). In this review, we not only have summarized the well-characterized roles of TRPV1, but also have highlighted the increasing importance of intracellular TRPV1-mediated pathways. Lastly, we have pointed out future research direction for answering several important questions that have remained unanswered. Vigorous investigation of the emerging roles of intracellular TRPV1 can allow a better understanding of how TRPV1 controls the cellular calcium homeostasis and its role in various physiological and pathophysiological conditions. J. Cell. Physiol. 232: 1957-1965, 2017. © 2016 Wiley Periodicals, Inc.

Versatile Roles of Intracellularly Located TRPV1 Channel.

https://repository.ust.hk/ir/bitstream/1783.1-78362/1/Ca2inStemCells.pdf

The role of Ca(2+) signaling on the self-renewal and neural differentiation of embryonic stem cells (ESCs)

Collagen remodeling by phagocytosis requires cell extension formation, which in turn involves interaction of the actin binding protein Flightless I (FliI) with non-muscle myosin IIA (NMMIIA) at cell-matrix adhesion sites. As Ca 2+ plays a central role in controlling actomyosin-dependent functions, we examined how Ca 2+ controls the generation of cell extensions and collagen remodeling. Ratio fluorimetry demonstrated localized Ca 2+ influx at extensions of fibroblasts. Western Blotting and qPCR showed high expression levels of the Ca 2+ -permeable, Transient Receptor Potential Vanilloid-4 (TRPV4) channel, which co-immunoprecipitated with β1 integrin and localized to adhesions. Blocking antibody to α2β1 integrin, the TRPV4-specific antagonist AB159908, or reduction of TRPV4 expression with siRNA, all blocked Ca 2+ influx. These treatments also inhibited interaction of FliI with NMMIIA, reduced the number and length of cell extensions and blocked collagen remodeling. Pull-down assays showed that Ca 2+ depletion inhibited interaction of purified FliI with NMMIIA filaments. Fluorescence resonance energy transfer experiments showed FliI-NMMIIA interactions require Ca 2+ influx. We conclude that Ca 2+ influx through TRPV4 channels regulates FliI-NMMIIA interactions, which in turn enable generation of the cell extensions essential for collagen remodeling.

/pdf/trpv4-mediates-the-calcium-influx-required-for-flightless-2fbcmoqdvg.pdf

TRPV4 mediates the calcium influx required for Flightless-non-muscle myosin interaction and collagen remodeling

TRP Channels in the Heart

Cytosolic Ca2+ ([Ca2+]i) is an important signal that regulates cardiomyocyte differentiation during cardiogenesis. TRPV1 is a Ca2+-permeable channel that is expressed in cardiomyocytes. In the present study, we utilized mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs) as a model to investigate the functional role of TRPV1 in cardiomyocyte differentiation. Induction of embryonic stem cells into cardiomyocytes was achieved using embryoid body (EB)-based differentiation method. Quantitative PCRs showed an increased TRPV1 expression during the differentiation process. In [Ca2+]i measurement study, application of TRPV1 agonists, capsaicin and camphor, elicited a [Ca2+]i rise in mESC-CMs, the effect of which was abolished by TRPV1-shRNA. In functional study, treatment of EBs with TRPV1 antagonists (capsazepine and SB366791) and TRPV1-shRNA reduced the size of the EBs and decreased the percentage of spontaneously beating EBs. TRPV1 antagonists and TRPV1-shRNA also suppressed the expression of cardiomyocyte marker genes, including cardiac actin, c-TnT, c-TnI, and α-MHC. Taken together, this study demonstrated an important functional role of TRPV1 channels in the differentiation of mESCs into cardiomyocytes.

/pdf/role-of-trpv1-in-the-differentiation-of-mouse-embryonic-stem-4ewe2kpp3j.pdf

Chun-Kit Wong

Papers

Role of TRPV1 in the differentiation of mouse embryonic stem cells into cardiomyocytes.