长链非编码RNA NKILA调控JAK2/STAT3通路加剧TGF-β1介导的肾纤维化

Renal interstitial fibrosis is a common pathological outcome of acute and chronic kidney disease. Within the present study, the aim was to explore whether long non‑coding RNA (lncRNA) NKILA regulates TGF‑β1‑induced renal tubular epithelial fibrosis through the JAK‑2/STAT3 pathway and its underlying mechanisms. A renal fibrosis model was established by treating HK‑2 cells with TGF‑β1. RNA sequencing revealed marked dysregulation of the cis‑regulated lncRNA NKILA, associated with the JAK2/STAT3 pathway. Functional studies involved overexpressing NKILA using lentivirus in HK‑2 cells with TGF‑β1‑treated cells as a control and knocking it down in the fibrotic model. The JAK2 inhibitor AG490 was employed for rescue experiments. Protein and mRNA levels of epithelial‑mesenchymal transition (EMT) markers [fibronectin, collagen I, epithelial (E)‑cadherin, α‑smooth muscle actin and vimentin] and JAK2/STAT3 pathway components were assessed using western blotting, immunofluorescence and reverse transcription‑quantitative PCR. Findings revealed that lncRNA NKILA overexpression promoted fibrosis of TGF‑β1‑treated HK‑2 cells by activating the JAK2/STAT3 pathway. While knockdown of lncRNA NKILA alleviated the TGF‑β1‑induced EMT damage in HK‑2 cells, downregulated EMT markers and upregulated E‑cadherin expression by suppressing the activation of the JAK2/STAT3 pathway. Of note, AG490 prevented the damaging effects of lncRNA NKILA or TGF‑β1‑induced HK‑2 cells. Mechanistically, lncRNA NKILA promoted TGF‑β1‑induced renal injuries by activating the JAK2/STAT pathway. Overall, this suggests that lncRNA NKILA functions as an independent fibrogenic factor and affects the progression of renal interstitial fibrosis by regulating the JAK2/STAT3 signaling pathway.