Diabetes, Metabolic Syndrome and Obesity (Jun 2023)

Profilin1 Promotes Renal Tubular Epithelial Cell Apoptosis in Diabetic Nephropathy Through the Hedgehog Signaling Pathway

  • Mai L,
  • He G,
  • Chen J,
  • Zhu J,
  • Chen S,
  • Yang H,
  • Zhang M,
  • Hou X,
  • Ke M,
  • Li X

Journal volume & issue
Vol. Volume 16
pp. 1731 – 1743

Abstract

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Liping Mai,1,* Guodong He,1,* Jing Chen,1 Jiening Zhu,1 Shaoxian Chen,1 Hui Yang,1 Mengzhen Zhang,1 Xinghua Hou,1 Miaola Ke,2 Xiaohong Li1,3 1Medical Research Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China; 2Department of Blood Transfusion, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 3Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaohong Li, Medical Research Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China, Email [email protected] Miaola Ke, Department of Blood Transfusion, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China, Email [email protected]: Profilin-1 (PFN1) regulates the dynamic balance of actin and plays an important role in cell functions as a hub protein in signaling molecule interaction networks. Dysregulation of PFN1 is related to pathologic kidney diseases. Diabetic nephropathy (DN) was recently reported as an inflammatory disorder, however, the molecular mechanisms of PFN1 in DN remain unclear. Therefore, the present study was conducted to explore the molecular and bioinformatic characteristics of PFN1 in DN.Methods: Bioinformatics analyses were performed on the chip of database in DN kidney tissues. A cellular model of DN was established in human renal tubular epithelial cells (HK-2) induced by high glucose. The PFN1 gene was overexpressed or knocked-down to investigate its function in DN. Flow cytometry was used to detect cell proliferation and apoptosis. PFN1 and proteins in the related signaling pathways were evaluated by Western blotting.Results: The expression of PFN1 was significantly increased in DN kidney tissues (P < 0.001) and was correlated with a high apoptosis-associated score (Pearson’s correlation = 0.664) and cellular senescence-associated score (Pearson’s correlation = 0.703). PFN1 protein was mainly located in cytoplasm. Overexpression of PFN1 promoted apoptosis and blocked the proliferation of HK-2 cells treated with high levels of glucose. Knockdown of PFN1 led to the opposite effects. Additionally, we found that PFN1 was correlated with the inactivation of the Hedgehog signaling pathway in HK-2 cells treated with high levels of glucose.Conclusion: PFN1 might play an integral role in the regulation of cell proliferation and apoptosis during DN development by activating the Hedgehog signaling pathway. This study provided molecular and bioinformatic characterizations of PFN1, and contributed to the understanding of the molecular mechanisms leading to DN.Keywords: PFN1, diabetic nephropathy, bioinformatic characterization, Hedgehog signaling pathway, apoptosis

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