Conclusion
The silencing of IGHG1 alleviated diabetic nephropathy by inhibiting the TRIM11/MEK/ERK axis and by downregulating TonEBP.
Methods
Bioinformatics analysis was conducted to screen the hub genes associated with diabetic nephropathy. The average human renal tubular epithelial cells were exposed to high glucose (HG) to generate an in vitro cell model. In addition, a mouse model of diabetic nephropathy was established using a high-fat diet and streptozotocin injection. Finally, the shRNA targeting immunoglobulin heavy constant gamma 1 (IGHG1) was introduced in vitro and in vivo to illustrate its effect on downstream factors and on the development diabetic nephropathy.
Results
Bioinformatics analysis revealed that IGHG1, TRIM11 (tripartite motif protein 11), and TonEBP are highly expressed in diabetic nephropathy. In vitro cell experiments demonstrated that IGHG1 positively regulates the expression of TRIM11 and TonEBP (tonicity-responsive enhancer binding protein) in HK2 cells treated with high glucose. Furthermore, TRIM11 upregulates the expression of TonEBP through activation of the MEK/ERK (mitogen-activated protein kinase/extracellular signal-regulated kinase) signaling pathway in HK2 cells treated with high glucose. In vivo, animal experiments further confirmed that silencing IGHG1 could prevent the occurrence and development of diabetic nephropathy.