ESM-1 Promotes the Process of Diabetic Nephropathy by Promoting the Expression of CXCL3.

Background: The analysis of diabetic nephropathy (DN)-related gene dataset demonstrated that C-X-C motif chemokine ligand 3 (CXCL3) is highly expressed in DN. Exploring the impact of CXCL3 in the course of DN is the core goal of this study.

Methods: The cell model used in this study was CIHP-1 cells induced by high glucose (HG). qRT-PCR and western blot analysis were carried out to determine the expression difference of CXCL3. After down-regulating the CXCL3 level, we analyzed HG-induced CIHP-1 cell viability by MTT assay, proliferation by EdU staining, apoptosis by flow cytometry, and changes in related protein expression by western blot. In order to analyze the possible regulatory relationship between endothelial cellspecific molecule 1 (ESM-1) and CXCL3 in DN, we constructed an over-expressed ESM-1 plasmid and carried out a rescue experiment.

Results: CXCL3 and ESM-1 were highly expressed in HG-induced podocytes (p<0.05). Silenced CXCL3 (siCXCL3) increased the viability and proliferation of CIHP- 1 cells induced by HG, reduced the proportion of apoptosis, and produced corresponding protein changes (p<0.01). After the overexpression of ESM-1, the effects of siCXCL3 were partially offset (p<0.05).

Discussion: This study reveals that ESM-1 exacerbates HG-induced podocyte injury by promoting CXCL3 expression, identifying a novel ESM-1/CXCL3 regulatory axis in DN progression. While the findings are derived from a specific cell model and the precise molecular mechanism requires further elucidation, consistent rescue experiments support this functional linkage. These results suggest that targeting the ESM-1/CXCL3 pathway may mitigate podocyte damage in DN, offering a potential therapeutic direction. Future studies should validate this axis in vivo and explore its clinical relevance.

Conclusion: In this study, ESM-1 increased HG-induced podocyte damage by promoting CXCL3 expression.