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논문분류	춘계학술대회 초록집
제목	STAT3 Inhibition Restores Dysregulation of Kidney Capillaries by Modulating Angiogenesis
저자	Kyuhyeon Kim
출판정보	2025; 2025(1):
키워드	STAT3, CKD, Glomerular Endothelial Cell, Angiogenesis, scRNA-seq
초록	Signal Transducer and Activator of Transcription 3 (STAT3) is a multifunctional transcription factor that regulates key cellular processes involved in renal fibrosis. Our previous studies showed that inhibiting STAT3 alleviates fibrosis by reducing inflammation and apoptosis. However, its role in angiogenesis, which maintains crucial capillary networks, remains unclear. In this study, we harnessed single-cell RNA sequencing (scRNA-seq) to explore the impact of STAT3 on angiogenesis in adenine-induced renal fibrosis. Adenine (2 mg/mouse, daily) and the STAT3 inhibitor Stattic (10 mg/kg, every other day) were administered to male C57BL/6 mice for 5 and 14 days to induce renal fibrosis. Kidneys and spleens were harvested for histological analysis and Western blotting. For scRNA-seq, RNA libraries were prepared with 14-day kidneys using the Illumina NovaSeq 6000 system. Differential gene expression analysis and downstream bioinformatics analysis were then conducted. STAT3 inhibition reduced serum creatinine levels elevated by adenine and restored kidney morphology. Histological analysis and Western blots confirmed that targeting STAT3 alleviated adenine-induced fibrosis, with decreased expression of pSTAT3 and pro-inflammatory markers. In the spleen, systemic inflammation markers were reduced. At the single-cell level, distinct kidney cell populations, including glomerular endothelial cells (GECs), were identified. STAT3 blockade restored kidney parenchymal cell populations while reducing fibroblasts and myeloid cells. Notably, the GEC population was significantly restored, exhibiting one of the strongest STAT3 pathway response and reestablished interactions with podocytes. Two GEC subpopulations, GEC0 and GEC1, were identified, with GEC1 showing enhanced angiogenesis-related gene expression and higher levels of gnaq and akap13, genes regulating endothelial function and proliferation, both reduced by inhibiting STAT3. CD31 staining revealed tubular atrophy and fragmentation in GECs from adenine-treated kidneys, while those under STAT3 inhibition appeared elongated and preserved integrity. Targeting STAT3 activity emerges as a promising therapeutic strategy for chronic kidney disease by restoring GEC composition and regulating angiogenesis.
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