Renal Integrins Under Metabolic Stress

Background: Integrins are transmembrane receptors that mediate extracellular matrix–cell interactions and play a central role in regulating epithelial integrity, mechano-transduction, and intracellular signaling. Obesity and metabolic stress are major risk factors for renal diseases and are known to induce extracellular matrix remodeling and cell–matrix signaling. However, how metabolic stress alters renal integrin expression in a sex-dependent manner remains poorly understood. In this study, we aim to evaluate the regulation of renal integrin expression under metabolic stress using diet-induced obesity in male and female mice. We hypothesize that high-fat diet alters renal integrin expression in a sex-specific manner. Methods: Male and female C57BL/6N mice were used for all experiments and fed ad libitum throughout the study. Initially, the mice were maintained on a standard laboratory diet (LabDiet 5001; referred to as low-fat diet, LFD) until they were about two months old. At around 11 to 12 weeks of age, the dietary intervention began: the mice were placed either on the low-fat diet (LFD) or switched to a 60% high-fat diet (Research Diets, D12492; HFD). After approximately six months on these respective diets, when the mice were around eight months old, kidneys were collected for analysis. The mouse body weights and insulin sensitivity or glucose tolerance measurements were recorded. Renal protein expression of integrin β1 and integrin α5 was quantified by Western blot analysis and normalized to α-tubulin. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to assess mRNA expression levels, with 18S ribosomal RNA serving as the internal control. Results: In female mice, integrin β1 expression was unchanged between the low-fat diet (LFD) and high-fat diet (HFD) groups (n = 3). In contrast, in male mice, integrin β1 expression was significantly elevated in the HFD group compared with LFD controls (P = 0.0173, n = 3). Integrin α5 expression was significantly increased in HFD-fed females compared with LFD controls (P = 0.0345, n = 4). However, integrin α5 expression in males remained unchanged across dietary conditions (n = 3). Basal renal integrin expression exhibited clear sex-dependent variation between male and female mice. Conclusion: These results show a clear sex-specific regulation of renal integrins under high-fat diet conditions, with integrin α5 increased in females and integrin β1 increased in males. This highlights intrinsic sexual dimorphism in kidney extracellular matrix signaling. Ongoing studies using integrin β1 knockdown and aging models will help define the causal role of integrin signaling under metabolic stress and support the development of precision strategies for kidney disease risk prediction and prevention. Acknowledgements: This program is supported by AHA under grant number 25AIREA1413883 and funded by NDSU RCA Economic Diversification Research Fund Sparking Big Ideas Seed Projects Program FAR0037405. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.