Table 4.
Mechanism of targeted regulation of PGRN in metabolic diseases.
| Target molecule | Molecular mechanism | Result | Disease | Refs |
|---|---|---|---|---|
| miR-29b-3p | Significantly inhibit the expression and release of PGRN, increase the expression of Bax, Caspase-3, MMP-1, MMP-13 and COL-X, reduce the transcription and secretion of col II, and inhibit the expression of Bcl-2. Recombinant PGRN can reduce the expression of Caspase-3 and Bax/Bcl-2 induced by miR-29b-3p. | Inhibition of chondrocyte apoptosis. | Cartilage and Bone homeostasis imbalance diseases Cartilage and Bone homeostasis imbalance diseases |
(148) |
| miR-29b-3p | Matrine can reduce the production of IL-6, IL-1β and TNF-α in chondrocytes, inhibit the expression of miR-29b-3p and increase the expression of PGRN. | Improve the viability of chondrocytes, inhibit cell apoptosis, and reduce joint tissue damage. | (149) | |
| LncRNA OIP5-AS1 | Inhibits the expression of miR-29b-3p, down regulates the expression of Bax, IL-6, IL-8 and TNF-α, and up regulates the expression of PGRN by sponging miR-29b-3p. | Promote the proliferation and migration of chondrocytes, inhibit the apoptosis and inflammation of chondrocytes, and improve the injury of chondrocytes. | (154) | |
| Atsttrin | By relying on TNFR2, Atsttrin strongly activated Akt pathway, slightly activated ERK1/2 pathway, and significantly increased the expression of cartilage marker genes Sox9, COL-II and Aggrecan. | Promote the anabolism of chondrocytes | (158, 159) | |
| Reduced the expression of inflammatory factors such as TNF-α, MMP-13, COX-2, iNOS and IL-17. | Alleviates the inflammatory reaction mediated by TNF-α and prevents intervertebral disc degeneration | (160) | ||
| By interacting with TNFR2, the expression of TNF-α, TNFR1, TNFR2, Bax, MMP-13 and Cathepsin K was decreased, and the expression of Bcl-2 was increased | Intervertebral disc degeneration score was significantly improved, intervertebral disc space stenosis and NP signal and cartilage loss were weakened | (161) | ||
| The transcription levels of ALP, COL1A1, OCN, OPN and Runx2 were up-regulated, and the formation and accumulation of TNF-α were decreased | Promote bone formation | (162) | ||
| Significantly decreased the expression of TNF-α, IL-6 and iNOS in BMSCs, and increased the expression of GAGs accumulation, calcium deposition, Col2a1, ACAN, Sox-9, Runx2, BMP-2, ALP, OCL, OCN, ALP and Col-I | Alleviates the inflammatory cascade, restores the balance of pro-inflammatory mediators, and stimulates cartilage repair and bone formation | (163) | ||
| By binding with TNFR1, Atsttrin down regulated the transcription levels of TNF-α, TRAP, CTSK and calcitonin receptor, and up-regulated the expressions of TNF-α, ALP, Runx2 and Col-I. By binding with TNFR2, Atsttrin activates Akt and ERK1/2 pathways and further increases the transcriptional expression of bone morphogenetic proteins Runx2, ALP and Col-I. |
Inhibited OC differentiation, promoted ob differentiation, and maintained OB-OC balance | (164) |