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ALK7 Knockdown Plays a Protective Role on HG-Stimulated MCs through Activation of the Nrf2/HO-1 Pathway
1Department of Endocrinology, Shaanxi Provincial People's Hospital, Xi'an 710068, China.
Objective:
Activin receptor-like kinase 7 (ALK7) is a member of the ALK family that has a key role in diabetes. However, the role of ALK7 in diabetic nephropathy (DN) remains unclear.
Methods:
Herein, we evaluated the effects of ALK7 on mesangial cells (MCs). MCs were transfected with si-ALK7 or pcDNA3.0-ALK7, and then stimulated with 40 mM glucose for 24 h. Cell proliferation was detected by MTT assay. Relative ROS level was detected using DCFH-DA staining. The contents of inflammatory cytokines were determined by ELISA. Western blot analysis was used to determine the expression levels of FN, Col IV, Nrf2, and HO-1 in MCs.
Results:
Our results showed that ALK7 expression was induced by HG in MCs. Knockdown of ALK7 inhibited HG-induced cell proliferation. The HG-induced ROS was mitigated by si-ALK7 with decreased ROS level and NOX activity. In addition, ALK7 knockdown exhibited anti-inflammatory activity in HG-stimulated MCs. Moreover, ALK7 knockdown attenuated fibronectin (FN) and collagen IV (Col IV) expression in MCs. Knockdown of ALK7 enhanced Nrf2/HO-1 pathway in MCs. Inhibition of Nrf2 reversed the protective effects of ALK7 knockdown on HG-stimulated MCs.
Conclusion:
ALK7 knockdown exerted protective effects on HG-stimulated MCs through activation of the Nrf2/HO-1 pathway. Thus, targeting ALK7 might be a therapeutic approach for the treatment of DN.
Insights
Knocking down Activin receptor-like kinase 7 (ALK7) protects kidney cells from high glucose damage by reducing inflammation and fibrosis. This suggests ALK7 is a potential therapeutic target for diabetic nephropathy.
Area of Science:
- Nephrology
- Endocrinology
- Molecular Biology
Background:
- Activin receptor-like kinase 7 (ALK7) plays a role in diabetes.
- The specific role of ALK7 in diabetic nephropathy (DN) is not well understood.
Purpose of the Study:
- To investigate the effects of ALK7 on mesangial cells (MCs) under high glucose conditions.
- To explore ALK7 as a potential therapeutic target for DN.
Main Methods:
- MCs were transfected with si-ALK7 or pcDNA3.0-ALK7.
- Cells were stimulated with high glucose (HG).
- Assays included MTT, DCFH-DA staining, ELISA, and Western blot to assess proliferation, ROS, inflammatory cytokines, and protein expression (FN, Col IV, Nrf2, HO-1).
Main Results:
- HG induced ALK7 expression in MCs.
- ALK7 knockdown inhibited HG-induced proliferation, ROS production, and inflammatory cytokine release.
- ALK7 knockdown reduced fibronectin and collagen IV expression.
- ALK7 knockdown enhanced the Nrf2/HO-1 pathway, and Nrf2 inhibition reversed these protective effects.
Conclusions:
- ALK7 knockdown protects MCs from HG-induced damage via the Nrf2/HO-1 pathway.
- Targeting ALK7 presents a potential therapeutic strategy for diabetic nephropathy.
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