#4996 TPPP3 REGULATES THE MICROTUBULE ACETYLATION AND PROMOTING YAP NUCLEAR RECRUITMENT IN HUMAN PODOCYTES

Abstract Background and Aims Minimal change disease (MCD) is a podocytopathy more commonly seen in children, but it also accounts for 10%–25% of adult NS. Patients with MCD manifest with abundant albuminuria, which is related to the damage of the glomerular filtration barrier. Podocytes are major components of the glomerular filtration barrier and play a crucial role in maintaining the integrity of the glomerular filtration barrier. Alterations in podocyte actin critically affect podocyte function. Tubulin polymerization-promoting protein family member 3 (TPPP3) is regulator of microtubule dynamic that has microtubule bundling activity. However, the mechanism of TPPP3 involved in podocyte apoptosis is remains unknown. Method Single-cell RNA sequencing comprehensively characterized the expression of TPPP3 in human glomeruli. We cultured human immortalized podocyte cells (HPC) in vitro, and constructed the HPC injury model. Immunofluorescence, western blot were used to determine the expression of TPPP3, α-tubulin, acetylated tubulin, phosopho-YAP1, Podocyte apoptosis was determined by Annexin V APC Apoptosis Detection Kit. Results TPPP3 was specifically expressed in human glomerular podocytes, and its expression level was significantly decreased in the cases of MCD and ADR induced podocyte injury(P<0.05). Knockdown of TPPP3 leaded to decreasing expression of acetylated tubulin in podocytes(P<0.05). Phosopho-YAP1 was also observed in the TPPP3 knockdown HPCs(P<0.05). Apoptosis was increased in the TPPP3 knockdown HPCs, suggesting TPPP3 may be related to the podocytes injury and apoptosis. Conclusion TPPP3 is involved with the apoptosis of podocytes by regulates nuclear recruitment of YAP which was promoted by microtubule acetylation.