| First Author | Ma S | Year | 2019 |
| Journal | Am J Physiol Renal Physiol | Volume | 317 |
| Issue | 3 | Pages | F623-F631 |
| PubMed ID | 31339777 | Mgi Jnum | J:283971 |
| Mgi Id | MGI:6382370 | Doi | 10.1152/ajprenal.00069.2019 |
| Citation | Ma S, et al. (2019) Knockout of TRPA1 exacerbates angiotensin II-induced kidney injury. Am J Physiol Renal Physiol 317(3):F623-F631 |
| abstractText | Macrophage-mediated inflammation plays a critical role in hypertensive kidney disease. Here, we investigated the role of transient receptor potential ankyrin 1 (TRPA1), a sensor of inflammation, in angiotensin II (ANG II)-induced renal injury. Subcutaneous infusion of ANG II (600 ng.min(-1).kg(-1)) for 28 days was used to induce hypertension and renal injury in mice. The results showed that ANG II-induced hypertensive mice have decreased renal Trpa1 expression (P < 0.01), whereas ANG II receptor type 1a-deficient hypotensive mice have increased renal Trpa1 expression (P < 0.05) compared with their normotensive counterparts. ANG II induced similar elevations of systolic blood pressure in Trpa1(-/-) and wild-type (WT) mice but led to higher levels of blood urea nitrogen (P < 0.05), serum creatinine (P < 0.05), and renal fibrosis (P < 0.01) in Trpa1(-/-) mice than WT mice. Similarly, ANG II increased both CD68(+)/inducible nitric oxide synthase(+) M1 and CD68(+)/arginase 1(+) M2 macrophages in the kidneys of both Trpa1(-/-) and WT mice (all P < 0.01), with higher extents in Trpa1(-/-) mice (both P < 0.01). Compared with WT mice, Trpa1(-/-) mice had significantly increased expression levels of inflammatory cytokines and their receptors in the kidney. Cultured murine macrophages were stimulated with phorbol 12-myristate 13-acetate, which downregulated gene expression of TRPA1 (P < 0.01). A TRPA1 agonist, cinnamaldehyde, significantly inhibited phorbol 12-myristate 13-acetate-stimulated expression of IL-1beta and chemokine (C-C motif) ligand 2 in macrophages, which were attenuated by pretreatment with a TRPA1 antagonist, HC030031. Furthermore, activation of TRPA1 with cinnamaldehyde induced apoptosis of macrophages. These findings suggest that TRPA1 may play a protective role in ANG II-induced renal injury, likely through inhibiting macrophage-mediated inflammation. |
