RT info:eu-repo/semantics/article
T1 Hippo Signaling Regulates High-NaCl-Induced Increase in RORγt+ Pro-Inflammatory Lymphocytes
A1 Zeeb, Bastian Lukas
A1 Weber-Stiehl, Saskia
A1 Escudero Hernández, Celia
A1 Müller, Dominik N.
A1 Maifeld, Andras
A1 Sommer, Felix
A1 Schmitt, Roland
A1 Sievers, Laura Katharina
K1 Biología celular
K1 Inmunología
K1 Bioquímica
K1 Nutrición
K1 Hipertensión
K1 Linfocito
K1 NaCl
K1 Sodio
K1 Vía hipo
K1 Th17
K1 TAZ
K1 2412 Inmunología
K1 2415 Biología Molecular
K1 3207 Patología
AB 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.
PB MDPI
SN 1422-0067
YR 2025
FD 2025
LK https://uvadoc.uva.es/handle/10324/83345
UL https://uvadoc.uva.es/handle/10324/83345
LA eng
NO International Journal of Molecular Sciences, 2025, vol. 26, n. 5.
NO Producción Científica
DS UVaDOC
RD 28-mar-2026