Effect of interfering Itgb6 gene expression on renal proximal tubular epithelial cells during hypoxia/reoxygenation injury
Integrin avß6 holds promise as a therapeutic target for organ fibrosis, yet targeted therapies are hampered by inflammatory-related side effects. Here, we revealed that upregulated avß6 in proximal tubule cells (PTCs) is remarkably positively correlated with renal inflammation both in CKD patients and in murine model of ischemia-reperfusion injury (IRI)-induced renal fibrosis. Knockout of avß6 significantly reduced the inflammatory response in IRI kidneys, especially the infiltration of pro-inflammatory macrophages. To delve deeper into the mechanism by which avß6 modulates inflammatory response, an unbiased RNA-sequencing of si-NC and si-Itgb6-transfected hypoxic TKPTS cells was performed. Overall design: TKPT cells were exposed to a hypoxic incubator (1% O2, 5% CO2, 96% N2, 37°C) for 24 h, and then the cells were placed back into a normal oxygen incubator (5% CO2, 37°C) for 12 h. When TKPT cells were cultured in 6-well culture plates to a density of 60%, RNA transfection reagent was used as a carrier to transfect TKPT cells with Itgb6 siRNA. An unbiased RNA-sequencing of si-NC and si-Itgb6-transfected hypoxic TKPTS cells was performed.