Selective tubular activation of hypoxia-inducible factor-2 alpha hasdual effects on renal fibrosis
| Autor: | Tae Hyun Yoo, Duk Hee Kang, Seung Jung Kim, Bo Young Nam, Kyoung Hye Kong, Vera Eremina, Kyu Bok Choi, Minsuk Kim, Jung Tak Park, Youn Hee Choi, Dong Ryeol Ryu, Shin Wook Kang, Beom Jin Lim, Kyoung Sook Park, Shina Lee, Ki Hwan Han, Susan E. Quaggin, Seung Hyeok Han, Kihwan Kwon, Hyung Jung Oh |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Transcriptional Activation medicine.medical_specialty 030232 urology & nephrology lcsh:Medicine Renal function Mice Transgenic Kidney Function Tests urologic and male genital diseases Article 03 medical and health sciences Mice 0302 clinical medicine Fibrosis Internal medicine Renal fibrosis medicine Basic Helix-Loop-Helix Transcription Factors Animals Humans lcsh:Science Hypoxia Renal stem cell Multidisciplinary business.industry lcsh:R Glomerulonephritis Epithelial Cells Glomerulonephritis IGA Hypoxia (medical) Middle Aged medicine.disease Disease Models Animal 030104 developmental biology Endocrinology Kidney Tubules Hypoxia-inducible factors Disease Progression lcsh:Q Kidney Diseases medicine.symptom Atrophy business Biomarkers Kidney disease |
| Zdroj: | SCIENTIFIC REPORTS(7) Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) |
| Popis: | Hypoxia-inducible factor (HIF) is a key transcriptional factor in the response to hypoxia. Although the effect of HIF activation in chronic kidney disease (CKD) has been widely evaluated, the results have been inconsistent until now. This study aimed to investigate the effects of HIF-2α activation on renal fibrosis according to the activation timing in inducible tubule-specific transgenic mice with non-diabetic CKD. HIF-2α activation in renal tubular cells upregulated mRNA and protein expressions of fibronectin and type 1 collagen associated with the activation of p38 mitogen-activated protein kinase. In CKD mice, activation of HIF-2α at the beginning of CKD significantly aggravated renal fibrosis, whereas it did not lead to renal dysfunction. However, activation at a late-stage of CKD abrogated both renal dysfunction and fibrosis, which was associated with restoration of renal vasculature and amelioration of hypoxia through increased renal tubular expression of VEGF and its isoforms. As with tubular cells with HIF-2α activation, those under hypoxia also upregulated VEGF, fibronectin, and type 1 collagen expressions associated with HIF-1α activation. In conclusion, late-stage renal tubular HIF-2α activation has protective effects on renal fibrosis and the resultant renal dysfunction, thus it could represent a therapeutic target in late stage of CKD. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|