A TRP to cardiac fibroblast differentiation

Thodeti, Charles K.; Paruchuri, Sailaja; Meszaros, J. Gary

doi:10.4161/chan.24328

Cited by 45 publications

(30 citation statements)

References 31 publications

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“…225 TRP channels are ubiquitously expressed in all cell types, providing calcium entry pathways and regulating a wide range of Ca 2+ -dependent cell functions 226 . Although in vitro studies have implicated TRPV4 227 and TRPM7 228 channels in cardiac myofibroblast transdifferentiation, their in vivo role is unclear.…”

Section: The Reparative and Proliferative Phasementioning

confidence: 99%

The Biological Basis for Cardiac Repair After Myocardial Infarction

Prabhu

Frangogiannis

2016

Circulation Research

1,504

1,404

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In adult mammals, massive sudden loss of cardiomyocytes following infarction overwhelms the limited regenerative capacity of the myocardium, resulting in formation of a collagen-based scar. Necrotic cells release danger signals, activating innate immune pathways and triggering an intense inflammatory response. Stimulation of toll-like receptor signaling and complement activation induces expression of pro-inflammatory cytokines (such as interleukin-1 and tumor necrosis factor-α) and chemokines (such as monocyte chemoattractant protein-1/CCL2). Inflammatory signals promote adhesive interactions between leukocytes and endothelial cells, leading to extravasation of neutrophils and monocytes. As infiltrating leukocytes clear the infarct from dead cells, mediators repressing inflammation are released, and anti-inflammatory mononuclear cell subsets predominate. Suppression of the inflammatory response is associated with activation of reparative cells. Fibroblasts proliferate, undergo myofibroblast transdifferentiation, and deposit large amounts of extracellular matrix proteins maintaining the structural integrity of the infarcted ventricle. The renin-angiotensin-aldosterone system and members of the transforming growth factor-β family play an important role in activation of infarct myofibroblasts. Maturation of the scar follows, as a network of cross-linked collagenous matrix is formed and granulation tissue cells become apoptotic. This review discusses the cellular effectors and molecular signals regulating the inflammatory and reparative response following myocardial infarction. Dysregulation of immune pathways, impaired suppression of post-infarction inflammation, perturbed spatial containment of the inflammatory response, and overactive fibrosis may cause adverse remodeling in patients with infarction contributing to the pathogenesis of heart failure. Therapeutic modulation of the inflammatory and reparative response may hold promise for prevention of post-infarction heart failure.

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Section: The Reparative and Proliferative Phasementioning

confidence: 99%

The Biological Basis for Cardiac Repair After Myocardial Infarction

Prabhu

Frangogiannis

2016

Circulation Research

1,504

1,404

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“…3) . Further in-depth analysis of TRPC6 function in various other cell types indicates that TRPC6 dysfunction plays a role in cardiac fibrosis, which might also contribute to renal fibrosis in TRPC6-associated FSGS (Nishida et al 2006, Davis et al 2012, Thodeti et al 2013).…”

Section: Trpc6mentioning

confidence: 99%

Renoprotection: focus on TRPV1, TRPV4, TRPC6 and TRPM2

et al. 2016

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Members of the transient receptor potential (TRP) cation channel receptor family have unique sites of regulatory function in the kidney which enables them to promote regional vasodilatation and controlled Ca influx into podocytes and tubular cells. Activated TRP vanilloid 1 receptor channels (TRPV1) have been found to elicit renoprotection in rodent models of acute kidney injury following ischaemia/reperfusion. Transient receptor potential cation channel, subfamily C, member 6 (TRPC6) in podocytes is involved in chronic proteinuric kidney disease, particularly in focal segmental glomerulosclerosis (FSGS). TRP vanilloid 4 receptor channels (TRPV4) are highly expressed in the kidney, where they induce Ca influx into endothelial and tubular cells. TRP melastatin (TRPM2) non-selective cation channels are expressed in the cytoplasm and intracellular organelles, where their inhibition ameliorates ischaemic renal pathology. Although some of their basic properties have been recently identified, the renovascular role of TRPV1, TRPV4, TRPC6 and TRPM2 channels in disease states such as obesity, hypertension and diabetes is largely unknown. In this review, we discuss recent evidence for TRPV1, TRPV4, TRPC6 and TRPM2 serving as potential targets for acute and chronic renoprotection in chronic vascular and metabolic disease.

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“…Although the expression of some TRP channels can be detected by using RT-PCR and appears to be associated with cardiac fibrosis, many of them cannot be detected by using electrophysiological recordings (6,30). Du and colleagues have found that silencing TRPM7 greatly diminishes the endogenous TRPM7 currents and Ca 2+ influx, which impairs the sensitivity of human atrial fibroblasts to TGF-b1-induced proliferation and differentiation.…”

Section: +mentioning

confidence: 99%