The mammalian superfamily of transient receptor potential (TRP) channels covers 28 members grouped in six families: TRPC, with C for “canonical”; TRPA, with A for “ankyrin”; TRPM, with M for “melastatin”; TRPML, with ML for “mucolipidin”; TRPP, with P for “polycystin”; and TRPV, with V for “vanilloid”. They all share a structure of six transmembrane (TM) regions, with a pore domain between TM5 and 6 and cytoplasmic amino-and carboxyl-termini. Functionally non-selective, Ca2+ permeant TRP channels are tetramers, which consist of the same or different TRP monomers, preferentially from the same family. While equipped with a≥ 10,000-fold transmembrane concentration gradient, Ca2+ influx through open Ca2+-permeant TRP channels serves a dual role by (i) sustaining the activation of intracellular enzymes and plasma membrane ion channels and (ii) continuously replenishing the endoplasmic reticulum Ca2+ supply for consistent and repetitive physiological functions. This latest Research Topic of Frontiers in Molecular Biosciences on TRP signal transduction has centered its discussion on two Ca2+-permeant TRP channels, namely, TRPA1, and TRPV1.

TRPA1 is the only member of the TRPA family and contains a characteristic high number of N-terminal ankyrin repeats (16 in humans), from which it derives its name. Ankyrin repeats are 33-amino acid motifs, which are found in many proteins where they mediate protein–protein interactions. The channel was originally cloned in human fibroblasts, where it inhibits fibroblast-to-myofibroblast differentiation, a hallmark of lung fibrosis. Myofibroblasts produce the extracellular matrix (ECM), which is important for cell barrier function but inhibits gas exchange in patients suffering from pulmonary fibrosis. Next to these cells, chondrocytes also produce ECM to keep the cartilage environment stable, which is, however, seriously damaged during osteoarthritis (OA), a chronic inflammatory destruction of joints. The authors of a manuscript of this Research Topic tested the hypothesis of whether activation of TRPA1 by one of its agonists, allyl isothiocyanate (AITC), changes the secretion of ECM and inflammation-related interleukins (Che et al.). Indeed, TRPA1 protein and mRNA were upregulated in the cartilages of patients with OA, and their chondrocytes developed a different swollen shape corresponding to a