Fraxin represses NF-κB pathway via inhibiting the activation of epidermal growth factor receptor to ameliorate diabetic renal tubulointerstitial fibrosis.

Renal tubulointerstitial fibrosis (RIF), featured by epithelial-to-mesenchymal-transition (EMT) of renal tubular epithelial cells and collagen deposition in the renal interstitial region, is the main pathological change of diabetic nephropathy (DN). Fraxin, the main active component of Fraxinus rhynchophylla Hance with anti-inflammatory activity, has been demonstrated to ameliorate glomerulosclerosis. However, the regulatory role of Fraxin on diabetic RIF remains unclear. In this study, we investigated the renal protective benefits of Fraxin against diabetic RIF and elucidated its mechanisms. In vitro, Fraxin inhibited the abnormal expression of EMT-related markers and proinflammatory cytokines, improved cellular morphology, and subsequently reduced the extracellular matrix (ECM) production in high glucose (HG)-induced NRK-52E cells. In vivo, Fraxin effectively ameliorated renal function, inhibited the abnormal expression of EMT-related markers and proinflammatory cytokines, and reduced ECM deposition in renal tubule interstitium in db/db mice. Notably, Fraxin could directly bind to epidermal growth factor receptor (EGFR), which contributed to the inhibition of EGFR phosphorylation and counteracted the activation of c-Src/NF-κB pathway, eventually ameliorating RIF. Thus, Fraxin may be a potential drug candidate for treating DN.
Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled.
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