Resistin-Like Molecule Beta (RELM-β) Regulates Proliferation of Human Diabetic Nephropathy Mesangial Cells via Mitogen-Activated Protein Kinases (MAPK) Signaling Pathway

Abstract

BackgroundResistin-like molecule beta (RELM-β) has been reported to be associated with diabetic nephropathy (DN). However, the role of RELM-β in DN is poorly understood. This study was conducted to delineate the underlying mechanisms of action and to investigate the role of RELM-β in the primitive development of DN via MAPK signaling pathways.Material/MethodsLentivirus-mediated vectors and RNAi technology were used to establish the model of RELM-β up-regulated and down-regulated expression in human mesangial cells (HMCs). The proliferation of HMCs was detected through CCK-8 method. The cell cycle and cell proliferation of HMCs was detected through flow cytometry. The MAPKs pathway protein activity was detected through Western blotting.ResultsThe HMCs with up-regulated and down-regulated expression of RELM-β increased or decreased significantly at 2–3 days. The HMCs with high glucose intervention reversed the proliferation inhibition. The HMCs with exogenous glucose or RELM-β protein intervention partially reversed the cell cycle inhibition. Among the MAPKs pathway, the phosphorylation activity of p38MAPK and JNK increased or decreased and ERK1/2 did not change in the overexpression or inhibition of RELM-β. The p38 MAPK pathway inhibitor SB202190 significantly inhibited the proliferation of HMCs caused by overexpression of RELM-β. Up-regulated expression of RELM-β induced the phosphorylation of p38 MAPK, JNK in HMCs and promoted HMCs proliferation and participated in early DN through the MAPKs pathway.ConclusionsThe results provide evidence that RELM-β is a potential molecular target for the treatment of DN.

Cassia auriculata leaf extract ameliorates diabetic nephropathy by attenuating autophagic necroptosis via RIP‐1/RIP‐3‐p‐p38MAPK signaling

“…Resveratrol is a natural polyphenolic compound was proven to inhibit the p‐38 MAPK signalling to inhibit pro‐inflammatory cytokines (Zong et al., 2012). Compelling evidence suggests that the regulation of the MAPK pathway could manage DN caused by high glucose‐induced oxidative stress (Wang et al., 2015, 2017). Consistently, our data indicated that phosphorylated p38MAPK protein levels were upregulated in high glucose‐ induced RGE cells but downregulated by CALE in a dose‐dependent manner.…”

Retracted Article: Ligustrazine attenuates renal damage by inhibiting endoplasmic reticulum stress in diabetic nephropathy by inactivating MAPK pathways

“…31 The family includes ERK, JNK, p-38 and ERK5. 32 Inhibition of MAPK pathways was reported to attenuate DN in a great number of previous studies. 33,34 Moreover, study from Chen demonstrated that Lig alleviates acute pancreatitis by accelerating acinar cell apoptosis at early phase via the suppression on p38 and Erk MAPK pathways.…”

The Inflammatory Response Induced by RELMβ Upregulates IL-8 and IL-1β Expression in Bronchial Epithelial Cells in COPD

“…In addition, we also investigated the ERK1/2, JNK, and AKT signaling pathways and showed that RELMβ could not activate those signaling pathways. This is different from signaling pathways, such as p38 MAPK and JNK, that RELMβ can initiate in human thylakoid cells 29 and intestinal epithelial cells, 30 suggesting that there are differences in the signaling regulatory pathways regulated by RELMβ in different tissues.…”