Formyl peptide receptor 1 promotes podocyte injury through regulation of mitogen-activated protein kinase pathways

• Published in: Experimental biology and medicine (Maywood, N.J.) N.J.), 2022-01, Vol.247 (2), p.87-96
• Main Authors: Zhang, Jun, Ding, Ting, Tang, Dongxing, Wang, Jianping, Huang, Peng
• Format: Article
• Language: English
• Subjects: Animals; Calcium - metabolism; Calcium Signaling; Cell Line; Diabetes Mellitus, Experimental - metabolism; Diabetic Nephropathies - metabolism; MAP Kinase Signaling System; Mice; Original Research; Podocytes - metabolism; Podocytes - pathology; Rats; Rats, Sprague-Dawley; Receptors, Formyl Peptide - metabolism
• ISSN: 1535-3702; 1535-3699; 1535-3699
• DOI: 10.1177/15353702211047451

Podocyte injury contributes to glomerular injury and is implicated in the pathogenesis of diabetic nephropathy. Formyl peptide receptor (FPR) 1 is abundantly expressed in neutrophils and mediates intracellular transport of Ca 2+. Intracellular Ca 2+ regulates pathological process in renal podocyte and plays a role in diabetic nephropathy. However, the role of formyl peptide receptor 1 in podocyte injury of diabetic nephropathy has not been reported yet. Firstly, a rat model with diabetic nephropathy was established by streptozotocin injection, and a cell model was established via high glucose treatment of mouse podocytes (MPC5). Formyl peptide receptor 1 was enhanced in streptozotocin-induced rats and high glucose-treated MPC5. Secondly, streptozotocin injection promoted the glomerular injury with decreased nephrin and podocin. However, tail injection with adenovirus containing shRNA for silencing of formyl peptide receptor 1 attenuated streptozotocin-induced glomerular injury and the decrease in nephrin and podocin. Moreover, silencing of formyl peptide receptor 1 repressed cell apoptosis of podocytes in diabetic rats and high glucose-treated MPC5. Lastly, protein expression levels of p-p38, p-ERK, and p-JNK protein were up-regulated in streptozotocin-induced rats and high glucose-treated MPC5. Silencing of formyl peptide receptor 1 attenuated high glucose-induced increase in p-p38, p-ERK, and p-JNK in MPC5, and over-expression of formyl peptide receptor 1 aggravated high glucose-induced increase in p-p38, p-ERK, and p-JNK. In conclusion, inhibition of formyl peptide receptor 1 preserved glomerular function and protected against podocyte dysfunction in diabetic nephropathy.