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Knockout of KLF10 Ameliorated Diabetic Renal Fibrosis via Downregulation of DKK-1.
- Source :
-
Molecules (Basel, Switzerland) [Molecules] 2022 Apr 20; Vol. 27 (9). Date of Electronic Publication: 2022 Apr 20. - Publication Year :
- 2022
-
Abstract
- Diabetes-induced chronic kidney disease leads to mortality and morbidity and thus poses a great health burden worldwide. Krüppel-like factor 10 (KLF10), a zinc finger-containing transcription factor, regulates numerous cellular functions, such as proliferation, differentiation, and apoptosis. In this study, we explored the effects of KLF10 on diabetes-induced renal disease by using a KLF10 knockout mice model. Knockout of KLF10 obviously diminished diabetes-induced tumor growth factor-β (TGF-β), fibronectin, and type IV collagen expression, as evidenced by immunohistochemical staining. KLF10 knockout also repressed the expression of Dickkopf-1 (DKK-1) and phosphorylated β-catenin in diabetic mice, as evidenced by immunohistochemical staining and Western blot analysis. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) revealed that significantly decreased type IV collagen, fibronectin, and DKK-1 existed in KLF10 knockout diabetic mice compared with control diabetic mice. Moreover, knockout of KLF10 reduced the renal fibrosis, as shown by Masson's Trichrome analysis. Overall, the results indicate that depletion of KLF10 ameliorated diabetic renal fibrosis via the downregulation of DKK-1 expression and inhibited TGF-β1 and phosphorylated β-catenin expression. Our findings suggest that KLF10 may be a promising therapeutic choice for the treatment of diabetes-induced renal fibrosis.
- Subjects :
- Animals
Collagen Type IV metabolism
Down-Regulation
Early Growth Response Transcription Factors genetics
Early Growth Response Transcription Factors metabolism
Female
Fibronectins genetics
Fibronectins metabolism
Fibrosis
Humans
Male
Mice
Mice, Knockout
Transforming Growth Factor beta1 metabolism
beta Catenin genetics
beta Catenin metabolism
Diabetes Mellitus, Experimental metabolism
Diabetic Nephropathies metabolism
Kruppel-Like Transcription Factors genetics
Kruppel-Like Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1420-3049
- Volume :
- 27
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Molecules (Basel, Switzerland)
- Publication Type :
- Academic Journal
- Accession number :
- 35565995
- Full Text :
- https://doi.org/10.3390/molecules27092644