Jung Eun Nam1, So Yeon Jo2, Chul Woo Ahn3, Yu Sik Kim4. 1. Brain Korea 21 PLUS Project for medical Science, Yonsei University, Seoul, Republic of Korea. 2. Department of Medicine, the Graduate school of Yonsei University, Seoul, Republic of Korea. 3. Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, Seoul, Republic of Korea; Division of Endocrinology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. 4. Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: cromoton@yuhs.ac.
Abstract
AIMS: Baicalin, a flavonoid glycoside substance extracted from Scutellaria baicalensis Georgi, has been shown to exhibit multiple therapeutic properties owing to its anti-inflammatory effect. Diabetes is characterized by chronic hyperglycemia, inflammation and oxidative stress, which promote renal fibrosis and kidney failure. Although anti-fibrogenic effects of baicalin in lung and liver have been reported previously, no study has investigated its roles in renal fibrosis. Here, we demonstrated protective effects of baicalin against fibrogenic process in human kidney proximal tubular epithelial cells (HK-2) exposed to diabetic milieu. MAIN METHODS: To investigate the effects of baicalin on oxidative stress- and inflammation-induced fibrosis in HK-2 cells, protein and gene expressions of NF-κB- and STAT3-associated inflammatory molecules and TGFβ-associated extracellular matrix proteins were examined by western blotting, immunocytochemistry and qRT-PCR. To determine physiological changes of HK-2 exposed to diabetic milieu in response to baicalin, production of cAMP and cGMP and Ca2+ influx were measured. KEY FINDINGS: Baicalin attenuated oxidative stress- and inflammation-inudced IκB and JAK2 phosphorylations and, subsequent, NF-κB nuclear translocation and STAT3 phosphorylation. Consequently, it markedly reduced transactivation of NF-κB- and STAT3-associated inflammatory genes such as ICAM1, VCAM1, TGFβ, IL1β and MCP1, and protein expression of TGFβ-associated extracellular matrix proteins, such as fibronectin and collagen IV. These effects are, partially, attributed to its regulatory function of intracellular concentration of Ca2+ via interaction with type A γ-aminobutyric acid receptor. SIGNIFICANCE: This is the first study which investigated anti-fibrogenic effect of baicalin in human kidney cells, and our results highlight a potential therapeutic application of baicalin for diabetic nephropathy.
AIMS: Baicalin, a flavonoid glycoside substance extracted from Scutellaria baicalensis Georgi, has been shown to exhibit multiple therapeutic properties owing to its anti-inflammatory effect. Diabetes is characterized by chronic hyperglycemia, inflammation and oxidative stress, which promote renal fibrosis and kidney failure. Although anti-fibrogenic effects of baicalin in lung and liver have been reported previously, no study has investigated its roles in renal fibrosis. Here, we demonstrated protective effects of baicalin against fibrogenic process in human kidney proximal tubular epithelial cells (HK-2) exposed to diabetic milieu. MAIN METHODS: To investigate the effects of baicalin on oxidative stress- and inflammation-induced fibrosis in HK-2 cells, protein and gene expressions of NF-κB- and STAT3-associated inflammatory molecules and TGFβ-associated extracellular matrix proteins were examined by western blotting, immunocytochemistry and qRT-PCR. To determine physiological changes of HK-2 exposed to diabetic milieu in response to baicalin, production of cAMP and cGMP and Ca2+ influx were measured. KEY FINDINGS:Baicalin attenuated oxidative stress- and inflammation-inudced IκB and JAK2 phosphorylations and, subsequent, NF-κB nuclear translocation and STAT3 phosphorylation. Consequently, it markedly reduced transactivation of NF-κB- and STAT3-associated inflammatory genes such as ICAM1, VCAM1, TGFβ, IL1β and MCP1, and protein expression of TGFβ-associated extracellular matrix proteins, such as fibronectin and collagen IV. These effects are, partially, attributed to its regulatory function of intracellular concentration of Ca2+ via interaction with type A γ-aminobutyric acid receptor. SIGNIFICANCE: This is the first study which investigated anti-fibrogenic effect of baicalin in human kidney cells, and our results highlight a potential therapeutic application of baicalin for diabetic nephropathy.