Suppression of renal fibrosis by galectin-1 in high glucose-treated renal epithelial cells

• Published in: Experimental cell research Vol. 316; no. 19; pp. 3282 - 3291
• Main Authors: Okano, Kazuhiro, Tsuruta, Yuki, Yamashita, Tetsuri, Takano, Mari, Echida, Yoshihisa, Nitta, Kosaku
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.11.2010; Elsevier BV
• Subjects: 60 APPLIED LIFE SCIENCES; Cell Line; Cellular biology; COLLAGEN; Collagen - genetics; Collagen - metabolism; Collagen Type I; Diabetes; DISEASES; Epithelial Cells - drug effects; Epithelial Cells - enzymology; Epithelial Cells - metabolism; Epithelial Cells - pathology; Extracellular Signal-Regulated MAP Kinases - metabolism; FIBROSIS; Galectin 1 - metabolism; Galectin-1; GLUCOSE; Glucose - pharmacology; GROWTH FACTORS; Humans; INHIBITION; Kidney - drug effects; Kidney - enzymology; Kidney - metabolism; Kidney - pathology; Kidney diseases; KIDNEYS; Kinases; Matrix Metalloproteinase 1 - genetics; Matrix Metalloproteinase 1 - metabolism; Mitogen-activated protein kinase; Models, Biological; Protein Transport - drug effects; Renal fibrosis; Signal transduction; Smad3; Smad3 Protein - metabolism; STIMULATION; TGF-β1; TRANSCRIPTION; Transcription, Genetic - drug effects; TRANSLOCATION; Mitogen-activated protein kinase; Galectin-1; TGF-β1; Smad3; Diabetes; Renal fibrosis
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2010.08.015

Diabetic nephropathy is the most common cause of chronic kidney disease. We investigated the ability of intracellular galectin-1 (Gal-1), a prototype of endogenous lectin, to prevent renal fibrosis by regulating cell signaling under a high glucose (HG) condition. We demonstrated that overexpression of Gal-1 reduces type I collagen (COL1) expression and transcription in human renal epithelial cells under HG conditions and transforming growth factor-β1 (TGF-β1) stimulation. Matrix metalloproteinase 1 (MMP1) is stimulated by Gal-1. HG conditions and TGF-β1 treatment augment expression and nuclear translocation of Gal-1. In contrast, targeted inhibition of Gal-1 expression reduces COL1 expression and increases MMP1 expression. The Smad3 signaling pathway is inhibited, whereas two mitogen-activated protein kinase (MAPK) pathways, p38 and extracellular signal-regulated kinase (ERK), are activated by Gal-1, indicating that Gal-1 regulates these signaling pathways in COL1 production. Using specific inhibitors of Smad3, ERK, and p38 MAPK, we showed that ERK MAPK activated by Gal-1 plays an inhibitory role in COL1 transcription and that activation of the p38 MAPK pathway by Gal-1 plays a negative role in MMP1 production. Taken together, two MAPK pathways are stimulated by increasing levels of Gal-1 in the HG condition, leading to suppression of COL1 expression and increase of MMP1 expression.