Fibroblast Growth Factor 2 Attenuates Renal Ischemia-Reperfusion Injury via Inhibition of Endoplasmic Reticulum Stress

Abstract

Acute kidney injury (AKI) is a serious clinical disease that is mainly caused by renal ischemia-reperfusion (I/R) injury, sepsis, and nephrotoxic drugs. The pathologic mechanism of AKI is very complex and may involve oxidative stress, inflammatory response, autophagy, apoptosis, and endoplasmic reticulum (ER) stress. The basic fibroblast growth factor (FGF2) is a canonic member of the FGF family that plays a crucial role in various cellular processes, including organ development, wound healing, and tissue regeneration. However, few studies have reported the potential therapeutic effect of FGF2 in the repair of renal ischemic injury in the past two decades. In the present study, we investigated the protective effect of FGF2 on renal I/R injury using Sprague-Dawley and NRK-52E cells. Our results showed that FGF2 significantly attenuates the apoptosis of kidney tissues after I/R injury through the inhibition of excessive ER stress. Moreover, FGF2 also alleviated the excessive ER stress and apoptosis in cultured NRK-52E cells injured by tert-Butyl hydroperoxide (TBHP). Significantly, phosphatidylinositol 3-kinase (PI3K)-selective inhibitor LY294002 and mitogen-activated protein kinase kinase (MEK)-selective inhibitor U0126 were utilized in the present study to examine the protective mechanism of FGF2. Our in vitro experimental results confirmed that both LY294002 and U0126 largely abolished the protective effect of FGF2. Taken together, the findings of the present study indicated that FGF2 attenuates I/R-induced renal epithelial apoptosis by suppressing excessive ER stress via the activation of the PI3K/AKT and MEK-ERK1/2 signaling pathways.

Plicosepalus acacia Extract and Its Major Constituents, Methyl Gallate and Quercetin, Potentiate Therapeutic Angiogenesis in Diabetic Hind Limb Ischemia: HPTLC Quantification and LC-MS/MS Metabolic Profiling

“…In experimental critical limb ischemia, therapeutic angiogenesis was mediated by combined actions of VEGF and FGF-2 [ 111 ]. FGF-2 was reported to inhibit endoplasmic reticulum stress and attenuate renal ischemia reperfusion injury [ 112 ].…”

Topical Application of Fibroblast Growth Factor 10-PLGA Microsphere Accelerates Wound Healing via Inhibition of ER Stress

“…Endoplasmic reticulum stress-induced apoptosis has been implicated in the development of multiple diseases, and the ER stress and UPR are partly involved in cell apoptosis induced by translocation [ 44 ]. In our previous research, the FGF-2 could inhibit excessive ER stress by activating the PI3K/AKT and MEK-ERK1/2 signaling pathways, thereby reducing the apoptosis of renal epithelial cells induced by ischemia-reperfusion injury [ 45 ], and Li et al have also reported that the FGF-2 could inhibit the expression of CHOP in cancer cells induced by TM [ 46 ]. Therefore, we did not exclude that the FGF10-PLGA microspheres promote wound healing through inhibiting ER stress-mediated apoptosis.…”

Modulatory Effect of Myokines on Reactive Oxygen Species in Ischemia/Reperfusion

“…Additionally, treatment with both low and high molecular weight isoforms of FGF-2 protected cultured rat cardiomyocytes against doxorubicin-mediated oxidative stress [ 186 ], possibly via preventing the doxorubicin-induced decrease in NRF-2 and enhancing the subsequent upregulation of HO-1 [ 187 , 188 ]. Intraperitoneal administration of FGF-2 markedly alleviated I/R-induced kidney damage ( Table 4 ) [ 99 , 189 ]. The proposed mechanism of action might involve the attenuation of mitochondrial DNA damage as reflected by lowering the amounts of 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine generation of tubular cells in ischemic kidneys and inhibition of excessive ER-stress.…”