Endothelial Cell‐Secreted Semaphorin 3F Promotes Proximal Tubule Cell Maturation and Polarization

• DOI: 10.1096/fasebj.2022.36.s1.r4368
• Publication Date: 2022-05-03T08:19:46Z
• Authors: Paulo Caceres
• Keywords: 0301 basic medicine; 0303 health sciences; 03 medical and health sciences

Endothelial cells secrete trophic factors that contribute to the maturation of surrounding tissues. The notion microvasculature as niche for local differentiation and homeostasis has implication in diseases like diabetic kidney disease, which is lost at early stages. are known produce semaphorins (Sema) signal molecules target proximity. isoform Sema3F secreted by endothelial throughout body, it regulate angiogenesis an autocrine fashion. However, can potentially reach other neighboring cell types, particular proximal tubule, since this epithelium closely associated with peritubular capillaries. It not whether influences tubule homeostasis. We hypothesize Sema3F, turn promotes epithelial polarization. utilized human line RPTEC/hTERT these polarize trans-well permeable support 2 weeks, they retain expression apical-basolateral polarization proteins. To study role maturation, we co-culture them HUVEC. First, measured release from HUVEC ELISA observed 206 ± 3 pg Sema3F/cm2 /day. Next, determine promote monitored progressive acquisition trans-epithelial resistance a measure tight junction maturation. cells, developed was 11±3% higher 1 week, 27±5% weeks compared monoculture (p<0.05). test stimulates resistance, added 200ng/mL recombinant cultures. increased week (vehicle= 152±5 Ω/cm2 vs. Sema3F= 171±3 ; p<0.05) 150±2 182±4 p<0.05). Also, accelerated basolateral protein E-cadherin surface biotinylation over weeks. Finally, produced stimulate silenced via lentivirus-transduction silencing shRNAs. prevented stimulation while control shRNA transduction showed expected 7 days (monoculture= 222±4 coculture-shSema3F= 218±7 p=NS coculture-shControl= 231±8 conclude reaches These findings have relevance possible mechanism disease pathologies where compromised.