ABSTRACT
The article "Lixisenatide protects doxorubicin-induced renal fibrosis by activating wNF-κB/TNF-α and TGF-ß/Smad pathways", by N.-F. Guo, Y.-J. Cao, X. Chen, Y. Zhang, Y.-P. Fan, J. Liu, X.-L. Chen published in Eur Rev Med Pharmacol Sci 2019; 23 (9): 4017-4026. DOI: 10.26355/eurrev_201905_17832-PMID: 31115031 has been retracted by the Editor in Chief for the following reasons: This paper has been questioned on PubPeer (https://pubpeer.com/publications/983F02C9C18817139AE18497C359FA). In particular, concerns were raised about Figures 2A and 5A as the figures result to overlap with previously published papers. The Editorial Office has contacted the corresponding author of the article to provide a reply to the comments on PubPeer and check the raw data. Still, the journal has yet to receive a reply. Therefore, considering the comments released on PubPeer and the lack of response from authors, the Editor in Chief no longer relies on the data presented and decided to withdraw the manuscript. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17832.
ABSTRACT
OBJECTIVE: This study aimed to investigate the effects of prostaglandin E2 receptor subtypes 1 (EP1) and 2 (EP2) on endoplasmic reticulum (ER) stress induced by TGF-ß1 in mouse mesangial cells (MCs) and to explore its potential mechanisms. MATERIALS AND METHODS: Mouse mesangial cells were isolated and cultured. EP-siRNAs were transfected into mesangial cells for silencing EP1 and EP2. Mesangial cell proliferation was assessed by the CCK-8 method. Expression of PGE2 was measured by enzyme-linked immunosorbent assay (ELISA). GRP78, TRPC1, ERK1/2, and phospho-ERK1/2 levels were examined by Western blot. RESULTS: TGF-ß1 induced mesangial cell proliferation and increased PGE2 secretion. Besides, TGF-ß1 significantly upregulated GRP78 and TRPC1 expression at the protein level. Phospho-ERK1/2 protein amounts were also increased (p<0.05). Compared with the TGF-ß1 group, cell proliferation in the EP1-siRNA+TGF-ß1 group was reduced, while GRP78, TRPC1, and ERK1/2 protein amounts were downregulated (p<0.05). EP1 agonist significantly enhanced above changes and their activities (p<0.05). EP1 antagonist significantly attenuated the above changes (p<0.05). Compared with TGF-ß1 group, cell proliferation in EP2-siRNA+TGF-ß1 group was increased, while GRP78, TRPC1, and ERK1/2 protein amounts were increased (p<0.05). EP2 agonist significantly attenuated the above changes (p<0.05). CONCLUSIONS: EP1 receptor may increase TGF-ß1-induced cell damage by increasing the activities of GRP78, TRPC1, and ERK1/2 via ER stress. Meanwhile, the EP2 receptor may reduce TGF-ß1-induced cell damage by suppressing GRP78, TRPC1, and ERK1/2 activities, also via ER stress. EP1 inhibition and EP2 stimulation may be a therapeutic option for delaying renal fibrosis.
Subject(s)
Endoplasmic Reticulum Stress , Fibrosis/metabolism , Kidney Diseases/metabolism , Receptors, Prostaglandin E, EP2 Subtype/metabolism , Transforming Growth Factor beta1/metabolism , Animals , Cell Proliferation , Cells, Cultured , Endoplasmic Reticulum Chaperone BiP , Fibrosis/pathology , Kidney Diseases/pathology , Mice , Mice, Inbred C57BL , Receptors, Prostaglandin E, EP2 Subtype/geneticsABSTRACT
OBJECTIVE: The aim of this study was to investigate whether Lixisenatide, NF-kB/TNF-α, and TGF-ß/Smad pathways exert clear regulatory roles in doxorubicin-induced renal fibrosis in rats, and to explore the possible underlying mechanism. MATERIALS AND METHODS: 30 rats were randomly assigned into the sham group, the Doxorubicin (DOX) group and the Lixisenatide group, 10 in each group. Eight weeks after the specific animal procedure, serum and kidney samples of rats were collected. The serum levels of Cr and BUN were detected using relative commercial kits. The activities of malondialdehyde (MDA), total antioxidant capacity (T-AOC), catalase (CAT), reduced glutathione (GSH), and superoxide dismutase (SOD) in kidney homogenate were accessed using commercial kits. Meanwhile, pathological lesions in kidney tissues were evaluated by HE staining, immune-histochemical staining and TUNEL assay, respectively. Also, the protein levels of relative genes in NF-kB/TNF-α, and TGF-ß/Smad pathways in rat kidneys were determined by immune-histochemical staining and Western blot, respectively. RESULTS: Rats in the Lixisenatide group showed significantly lower levels of Cr and BUN. Activities of T-AOC, CAT, GSH, and SOD in the Lixisenatide group were significantly higher, whereas MDA activity was significantly lower than in the DOX group. Lixisenatide treatment remarkably alleviated DOX-induced pathological lesions and cell apoptosis in kidneys. Furthermore, the protein levels of relative genes in NF-kB/TNF-α and TGF-ß/Smad pathways in rat kidneys were significantly downregulated in the Lixisenatide group when compared with the DOX group. CONCLUSIONS: Lixisenatide protects doxorubicin-induced renal fibrosis in rats by inhibiting NF-κB/TNF-α and TGF-ß/Smad pathways.
