@article{oai:soar-ir.repo.nii.ac.jp:00020246,
 author = {Numaga-Tomita, Takuro and Kitajima, Naoyuki and Kuroda, Takuya and Nishimura, Akiyuki and Miyano, Kei and Yasuda, Satoshi and Kuwahara, Koichiro and Sato, Yoji and Ide, Tomomi and Birnbaumer, Lutz and Sumimoto, Hideki and Mori, Yasuo and Nishida, Motohiro},
 journal = {SCIENTIFIC REPORTS},
 month = {Dec},
 note = {Structural cardiac remodeling, accompanying cytoskeletal reorganization of cardiac cells, is a major clinical outcome of diastolic heart failure. A highly local Ca2+ influx across the plasma membrane has been suggested to code signals to induce Rho GTPase-mediated fibrosis, but it is obscure how the heart specifically decodes the local Ca2+ influx as a cytoskeletal reorganizing signal under the conditions of the rhythmic Ca2+ handling required for pump function. We found that an inhibition of transient receptor potential canonical 3 (TRPC3) channel activity exhibited resistance to Rho-mediated maladaptive fibrosis in pressure-overloaded mouse hearts. Proteomic analysis revealed that microtubule-associated Rho guanine nucleotide exchange factor, GEF-H1, participates in TRPC3-mediated RhoA activation induced by mechanical stress in cardiomyocytes and transforming growth factor (TGF) β stimulation in cardiac fibroblasts. We previously revealed that TRPC3 functionally interacts with microtubule-associated NADPH oxidase (Nox) 2, and inhibition of Nox2 attenuated mechanical stretch-induced GEF-H1 activation in cardiomyocytes. Finally, pharmacological TRPC3 inhibition significantly suppressed fibrotic responses in human cardiomyocytes and cardiac fibroblasts. These results strongly suggest that microtubule-localized TRPC3-GEF-H1 axis mediates fibrotic responses commonly in cardiac myocytes and fibroblasts induced by physico-chemical stimulation, Article, SCIENTIFIC REPORTS. 6: 39383(2016)},
 title = {TRPC3-GEF-H1 axis mediates pressure overload-induced cardiac fibrosis},
 volume = {6},
 year = {2016}
}