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| Item Type: | Article |
|---|---|
| Title: | Hippo signaling regulates high NaCl induced increase of RORγt+ pro-inflammatory lymphocytes |
| Creators Name: | Zeeb, B.L., Weber-Stiehl, S., Escudero-Hernández, C., Müller, D.N., Maifeld, A., Sommer, F., Schmitt, R. and Sievers, L.K. |
| Abstract: | Arterial hypertension is a major health challenge worldwide. Lifestyle factors including dietary NaCl increase the risk of hypertension. Pathophysiologically, the activation of the renin–angiotensin–aldosterone system and vascular remodeling, as well as the increase in Th17 lymphocytes, contribute to increased blood pressure and end-organ damage. To date, it is unknown whether NaCl, changed osmolarity, and/or angiotensin II directly induce Th17 differentiation, and, if so, which molecular pathways are involved. One major transcription factor inducing Th17 differentiation is RORγt. RORγt+ immune-cell subtypes increased in a mouse model of hypertension. In primary splenocytes, NaCl and mannitol but not angiotensin II increased the frequency of RORγt+ lymphocytes and IL-17 and IL-22 expression. NaCl and angiotensin II induced angiotensin II receptor expression. NaCl led to the inactivation of the Hippo pathway in lymphocytes and decreased phosphorylation of the transcription factor TAZ, leading to increased functionality as a transcriptional coregulator. Inhibition of TAZ by verteporfin blocked the NaCl-induced increase in RORγt+ lymphocytes. Taken together, we found that NaCl induced pro-inflammatory lymphocytes via the regulation of Hippo signaling. The results suggest the possible involvement of Hippo signaling in the pathophysiology of salt-sensitive hypertension, with the potential for therapeutic targeting by small-molecule approaches. |
| Keywords: | Hypertension, Lymphocyte, NaCl, Sodium, Hippo Pathway, Th17, TAZ, Animals, Mice |
| Source: | International Journal of Molecular Sciences |
| ISSN: | 1422-0067 |
| Publisher: | MDPI |
| Volume: | 26 |
| Number: | 5 |
| Page Range: | 2143 |
| Date: | March 2025 |
| Official Publication: | https://doi.org/10.3390/ijms26052143 |
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