2017
DOI: 10.1007/s00441-017-2754-1
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FSP1-specific SMAD2 knockout in renal tubular, endothelial, and interstitial cells reduces fibrosis and epithelial-to-mesenchymal transition in murine STZ-induced diabetic nephropathy

Abstract: Extracellular matrix deposition during tubulointerstitial fibrosis (TIF), a central pathological process in patients with diabetic nephropathy (DN), is driven by locally activated, disease-relevant myofibroblasts. Myofibroblasts can arise from various cellular sources, e.g., tubular epithelial cells via a process named epithelial-to-mesenchymal transition (EMT). Transforming growth factor beta 1 (TGF-β1) and its downstream Smad signaling play a critical role in both TIF and EMT. Whereas Smad3 is one central me… Show more

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Cited by 37 publications
(26 citation statements)
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“…The mice with constitutive deletion of Smad2 were embryonic lethal [44]. Conditional deletion of Smad2 could significantly attenuate renal fibrosis, tubular EMT-like changes and the levels of myofibroblast markers in diabetic nephropathy mice, as well as decreased Smad3 and TGF-β1 [45]. Besides, Smad2 deletion promoted fibrosis through enhanced TGF-β/Smad3 signaling, and increased autoinduction of TGF-β1.…”
Section: Tgf-β/smad Signaling Pathway In Renal Fibrosismentioning
confidence: 99%
“…The mice with constitutive deletion of Smad2 were embryonic lethal [44]. Conditional deletion of Smad2 could significantly attenuate renal fibrosis, tubular EMT-like changes and the levels of myofibroblast markers in diabetic nephropathy mice, as well as decreased Smad3 and TGF-β1 [45]. Besides, Smad2 deletion promoted fibrosis through enhanced TGF-β/Smad3 signaling, and increased autoinduction of TGF-β1.…”
Section: Tgf-β/smad Signaling Pathway In Renal Fibrosismentioning
confidence: 99%
“…Conversely, unlike Smad3, the function of Smad2 in DKD is unclear. Overexpression of Smad2 attenuated TGF-β1induced phosphorylated Smad3 and collagen expression, whereas deletion of Smad2 promoted renal fibrosis via substantially enhanced Smad3 signaling (Meng et al, 2010;Loeffler et al, 2018). Although Smad2 interacts with Smad3 physically, Smad2 and -3 may compete for phosphorylation in response to TGF-β1 stimulation.…”
Section: Smad-dependent Signaling Pathwaymentioning
confidence: 99%
“…In canonical TGF-β signaling, Smad2, and Smad3 are two key downstream mediators that are highly activated in the fibrotic kidney (Wang et al, 2006;Chung et al, 2010b;Zhou et al, 2010;Loeffler et al, 2018). Although Smad2 and Smad3 bind together, their functional roles are distinct.…”
Section: Distinct Roles Of Smad2 and Smad3 In Renal Fibrosismentioning
confidence: 99%
“…However, a recent finding that conditional deletion of Smad2 from TECs accelerates renal fibrosis reveals a protective role of Smad2 in renal fibrosis (Meng et al, 2010). In addition, FSP1-specific Smad2 knockout in renal tubular, endothelial, and interstitial cells is also reported to reduce renal fibrosis and epithelial-to-mesenchymal transition in murine streptozotocin (STZ)-induced diabetic nephropathy (Loeffler et al, 2018).…”
Section: Distinct Roles Of Smad2 and Smad3 In Renal Fibrosismentioning
confidence: 99%