Table 3.

Anti-fibrotic effects of GSK-3β in various organs/tissues.

Models	Organs/Tissues	Outcomes	References
C57BL/6 mice	Heart	Piperine treatment inhibits the conversion of cardiac fibroblasts to myofibroblasts, reduces α-SMA and collagen accumulation, and eventually alleviates cardiac hypertrophy and fibrosis.	82
Cardiac fibroblasts isolated from SD neonatal rats	Heart	SDT attenuates myocardial fibrosis by phosphorylating and activating GSK-3β at Tyr216. Meanwhile, α-SMA and COLI/COLIII are both decreased.	136
GSK-3β KO mice	Heart	Maintaining GSK-3β in an active state can inhibit fibrosis and limit maladaptation remodeling by transforming fibroblasts into myofibroblasts and accumulating ECM.	81
Human lung fibroblasts	Lung	In IPF fibroblasts, inactive GSK-3β promotes active β-catenin and pathological proliferation, and further enhances the pathological proliferation of fibroblasts and collagen polymerization.	17
Human adult lung fibroblasts	Lung	GSK-3β inhibitor promotes α-SMA expression and collagen production, and further induces the phenotypic transformation of human lung fibroblasts into myofibroblasts, leading to the pathophysiology of pulmonary fibrosis.	16
Male BALB/c mice	Lung	CIP4 silencing can effectively relieve diabetic pulmonary fibrosis through activation of GSK-3β, resulting in decreased levels of vimentin and α-SMA and increased levels of E-cadherin.	91
Human HSC line	Liver	Tβ4 inactivation inhibits liver fibrosis at least partially via activating the GSK-3β pathway, leading to the inhibition of HSC activation, transdifferentiation and collagen excessive accumulation.	99
C57BL/6 mice	Liver	GSK-3β activation reduces the levels of fibrosis markers, including α-SMA, COLI, and COLIII, thereby preventing the development of liver fibrosis in high fat diet-induced mice.	101
C57BL/6 mice	Kidney	Fingolimod downregulates the levels of α-SMA and collagen, prevents the formation of myofibroblasts, and reduces the synthesis of ECM protein by activating GSK-3β to repress the progression of renal fibrosis.	104
Rat renal proximal tubular epithelial cells	Kidney	UP incubation decreases E-cadherin expression, increases α-SMA expression, and the promotes morphological conversion to myofibroblast-like phenotype. However, sEH inhibitor AUDA treatment inhibits GSK-3β phosphorylation, thereby ameliorating EMT and renal fibrosis.	12
SGK1 KO mice	Kidney	Increased GSK-3β activity reduces α-SMA expression and collagen accumulation, thereby significantly inhibiting obstruction-induced EMT and renal fibrosis.	37
Human peritoneal mesothelial cells	Peritoneum	Activation of GSK-3β improves the effect on EMT and peritoneal fibrosis by inhibiting the α-SMA expression and restoring E-cadherin expression.	109
C57BL/6 mice	Intestine	GSK-3β activation significantly decreases the expression of α-SMA, COLI/III, and FN, further regulating the EMT process to exert a therapeutic effect in the intestine fibrosis.	110