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Yueling Guo, Edauardo Mascareno, M. A. Q. Siddiqui, P-362: Regulation of the renin-angiotensin system by JAK/STAT pathway, American Journal of Hypertension, Volume 14, Issue S1, April 2001, Pages 151A–152A, https://doi.org/10.1016/S0895-7061(01)01958-6
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Abstract
It is well documented that perturbation of the renin-angiotesin system (RAS) can be correlated with the development of systemic hypertension, cardiac hypertrophy and cardiac failure. We have recently shown that the JAK/STAT signaling pathway plays a critical role in contribution of the cardiac tissue RAS where in the promoter of the prohormone angiotensiogen (ANG) serves as the target site for activated STAT proteins. In an attempt to understand the underlying mechanism(s), we performed the transient transfection by liver (Hep G2) cells in culture with constitutive Jak2(TEL-Jak2) expression plasmid and the ANG-luciferase reporter DNA. We observed that Jak2 overexpression stimulated the ANG promoter activity by 5-fold. Jak2 dependent ANG promoter function required an intact ST-domain, the STAT-binding sequence, as ANG/luciferase plasmid with mutated ST-domain was unresponsive. Furthermore, administration of tyrphostin AG-490, a potent inhibitor of Jak2 phosphorylation resulted in loss of Jak2 dependent stimulation of ANG promoter. Thus, it appears that activation of Jak2 constitutes the primary signaling event responsible for STAT mediated stimulation of the RAS.