CD38 knockout attenuates type 2 diabetic renal injury by downregulating p53 and Bax via the ERK/JNK signaling pathway.
Diabetic nephropathy (DN), the leading cause of end-stage renal disease (ESRD), imposes substantial burdens on patients' health and socioeconomic status. Although current therapies targeting blood pressure, glycemic control, and the renin-angiotensin system provide partial relief for DN, their efficacy remains limited. CD38, a 46-kilodalton type II transmembrane glycoprotein, is reported involved in the development of diabetes mellitus. However, the specific role and molecular mechanisms of CD38 in DN pathogenesis require further elucidation. This study aims to investigate these mechanisms.
Analyze the expression of CD38 in DN through the GEO database.Type 2 diabetic mouse models were established by using high-fat diet and streptozocin (STZ) injection. Four groups of mice were used in this experiment: WT group, DM group, CD38-/- group and CD38-/-+DM group. Body weight and fasting blood glucose were monitored longitudinally. After Post-euthanasia, kidney weight and body weight were weighed, then calculated kidney weight/body weight ratio. Renal tissues underwent histopathological evaluation (H&E, PAS, PAM staining) and molecular analyses (immunohistochemistry, RT-qPCR, Western blot).
CD38 expression was significantly higher (P < 0.05) in DN than in normal humans. And CD38 deletion ameliorated renal histopathological injury in type 2 diabetic mice in H&E staining, glycogen staining, PAM staining. RT-qPCR and Western blot results showed expressions of p53 and Bax in kidney tissues of CD38-/-+DM group mice was significantly decreased (P < 0.05) and Bcl-2 was significantly increased (P < 0.01) compared with that of the DM group mice. Bax expression was decreased and Bcl-2 expression was increased in the renal tissues of mice of CD38-/-+DM group when compared with mice in the DM group in immunohistochemical staining. CD38 deletion could alleviate ERK, JNK and p38 of MAPK signaling pathway(P < 0.05). Inhibition of ERK and JNK in high glucose condition ameliorated apoptosis by down-regulating p53 and Bax (P < 0.05).
CD38 deletion regulated body weight and fasting blood glucose, improved renal histopathological injury and apoptosis by inhibiting MAPK signaling pathway; CD38 deficiency alleviates diabetic nephropathy by inhibiting MAPK/p53-mediated apoptosis, highlighting its role as a potential therapeutic target.
Not applicable, and this study does not yet involve clinical data.
Analyze the expression of CD38 in DN through the GEO database.Type 2 diabetic mouse models were established by using high-fat diet and streptozocin (STZ) injection. Four groups of mice were used in this experiment: WT group, DM group, CD38-/- group and CD38-/-+DM group. Body weight and fasting blood glucose were monitored longitudinally. After Post-euthanasia, kidney weight and body weight were weighed, then calculated kidney weight/body weight ratio. Renal tissues underwent histopathological evaluation (H&E, PAS, PAM staining) and molecular analyses (immunohistochemistry, RT-qPCR, Western blot).
CD38 expression was significantly higher (P < 0.05) in DN than in normal humans. And CD38 deletion ameliorated renal histopathological injury in type 2 diabetic mice in H&E staining, glycogen staining, PAM staining. RT-qPCR and Western blot results showed expressions of p53 and Bax in kidney tissues of CD38-/-+DM group mice was significantly decreased (P < 0.05) and Bcl-2 was significantly increased (P < 0.01) compared with that of the DM group mice. Bax expression was decreased and Bcl-2 expression was increased in the renal tissues of mice of CD38-/-+DM group when compared with mice in the DM group in immunohistochemical staining. CD38 deletion could alleviate ERK, JNK and p38 of MAPK signaling pathway(P < 0.05). Inhibition of ERK and JNK in high glucose condition ameliorated apoptosis by down-regulating p53 and Bax (P < 0.05).
CD38 deletion regulated body weight and fasting blood glucose, improved renal histopathological injury and apoptosis by inhibiting MAPK signaling pathway; CD38 deficiency alleviates diabetic nephropathy by inhibiting MAPK/p53-mediated apoptosis, highlighting its role as a potential therapeutic target.
Not applicable, and this study does not yet involve clinical data.
Authors
Li Li, Du Du, Zhang Zhang, Fang Fang, You You, Fan Fan, Chen Chen, Fang Fang, Li Li
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