Activation of TRPA1 in Bladder Suburothelial Myofibroblasts Counteracts TGF-β1-Induced Fibrotic Changes

• Published in: International journal of molecular sciences 2023-05, Vol.24 (11), p.9501
• Main Authors: Zhao, Mengmeng, Ding, Ning, Wang, Haoyu, Zu, Shulu, Liu, Hanwen, Wen, Jiliang, Liu, Jiaxin, Ge, Nan, Wang, Wenzhen, Zhang, Xiulin
• Format: Article
• Language: English
• Subjects: allylisothiocyanate; Animals; Apoptosis; Bladder; bladder fibrosis; Collagen; Collagen (type I); Collagen (type III); Collagen Type III - metabolism; Crosstalk; Down-regulation; Fibroblasts; Fibroblasts - metabolism; Fibronectin; Fibronectins; Fibronectins - metabolism; Fibrosis; Gene expression; Growth factors; Humans; Immunocytochemistry; Injury prevention; Intestine; myofibroblasts; Myofibroblasts - metabolism; Phosphorylation; Protein expression; Proteins; Pulmonary fibrosis; Rats; RNA; RNA-mediated interference; SCI; Spinal cord injuries; TGF-β1; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-b1; Transforming growth factors; Transient receptor potential proteins; TRPA1 Cation Channel - genetics; TRPA1 Cation Channel - metabolism; TRPA1 channel; Urinary Bladder - pathology; Western blotting
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24119501

The activation of the transient receptor potential ankyrin 1 (TRPA1) channel has anti-fibrotic effects in the lung and intestine. Suburothelial myofibroblasts (subu-MyoFBs), a specialized subset of fibroblasts in the bladder, are known to express TRPA1. However, the role of the TRPA1 in the development of bladder fibrosis remains elusive. In this study, we use the transforming growth factor-β1 (TGF-β1) to induce fibrotic changes in subu-MyoFBs and assess the consequences of TRPA1 activation utilizing RT-qPCR, western blotting, and immunocytochemistry. TGF-β1 stimulation increased α-SMA, collagen type I alpha 1 chain(col1A1), collagen type III (col III), and fibronectin expression, while simultaneously suppressing TRPA1 in cultured human subu-MyoFBs. The activation of TRPA1, with its specific agonist allylisothiocyanate (AITC), inhibited TGF-β1-induced fibrotic changes, and part of these inhibition effects could be reversed by the TRPA1 antagonist, HC030031, or by reducing TRPA1 expression via RNA interference. Furthermore, AITC reduced spinal cord injury-induced fibrotic bladder changes in a rat model. The increased expression of TGF-β1, α-SMA, col1A1 and col III, and fibronectin, and the downregulation of TRPA1, were also detected in the mucosa of fibrotic human bladders. These findings suggest that TRPA1 plays a pivotal role in bladder fibrosis, and the negative cross talk between TRPA1 and TGF-β1 signaling may represent one of the mechanisms underlying fibrotic bladder lesions.