biostudies-literatureGonzalez-Gonzalez LConsejo Nacional de Ciencia y TecnologíaFundación Miguel Alemán, A.CSEP-CINVESTAV1994351https://www.ebi.ac.uk/biostudies/studies/S-EPMC9067463biostudies-literatureUnknown10(2)ZO-2 is a peripheral tight junction (TJ) protein whose silencing in renal epithelia induces cell hypertrophy. Here, we found that in ZO-2 KD MDCK cells, in compensatory renal hypertrophy triggered in rats by a unilateral nephrectomy and in liver steatosis of obese Zucker (OZ) rats, ZO-2 silencing is accompanied by the diminished activity of LATS, a kinase of the Hippo pathway, and the nuclear concentration of YAP, the final effector of this signaling route. ZO-2 appears to function as a scaffold for the Hippo pathway as it associates to LATS1. ZO-2 silencing in hypertrophic tissue is due to a diminished abundance of ZO-2 mRNA, and the Sp1 transcription factor is critical for ZO-2 transcription in renal cells. Treatment of OZ rats with metformin, an activator of Tissue barriersZO-2 favors Hippo signaling, and its re-expression in the steatotic liver by AMPK restores junctional sealing.PMC90674632018FORDECYT-PRONACES-140644/2020FIDSC2018/33Alvarez-Salas LMGaray EGallego-Gutierrez HHernandez-Guzman CRangel-Guerrero SIGonzalez-Gonzalez LAvelino-Cruz JEGutierrez-Ruiz MCMartin-Tapia DLopez-Bayghen EHernandez-Melchor DGonzalez-Mariscal LChavez-Munguia BfalseZO-2 favors Hippo signaling, and its re-expression in the steatotic liver by AMPK restores junctional sealing.ZO-2 is a peripheral tight junction (TJ) protein whose silencing in renal epithelia induces cell hypertrophy. Here, we found that in ZO-2 KD MDCK cells, in compensatory renal hypertrophy triggered in rats by a unilateral nephrectomy and in liver steatosis of obese Zucker (OZ) rats, ZO-2 silencing is accompanied by the diminished activity of LATS, a kinase of the Hippo pathway, and the nuclear concentration of YAP, the final effector of this signaling route. ZO-2 appears to function as a scaffold for the Hippo pathway as it associates to LATS1. ZO-2 silencing in hypertrophic tissue is due to a diminished abundance of ZO-2 mRNA, and the Sp1 transcription factor is critical for ZO-2 transcription in renal cells. Treatment of OZ rats with metformin, an activator of 2022-01-01T00:00:00Z2022 Apr2026-04-08T10:05:46.008Z2025-04-21T14:49:46.013ZS-EPMC90674633468970510.1080/21688370.2021.1994351