Table 3.

Mechanism of PGRN in diabetic complications.

Target molecule	Way	Molecular mechanism	Result	Disease	Refs
PGRN	Inflammation	PGRN+TNFR2: Activated Akt, ERK1/2 and mTOR, reduced the transcription levels of TNF-α, IL-1β, NOS2 and COX-2 and NOS2 protein levels, up-regulated the expression of col II and ACN, and inhibited the phosphorylation of p38, JNK and NF-κB induced by TNF-α.	By inhibiting the inflammatory reaction, the bone formation increased and the residual bone space decreased, which promoted the healing of DOP.	DOP	(134)
	Inflammation-Bone coupling	PGRN+TNFR2: Activated Akt and ERK1/2,reduced the expression of TNF-α, IL-1β, COX-2 and NOS2, inhibited p65 translocati-on and activation of JNK and p38, increa-sed BV/TV ratio, transcriptional levels of COL2A1 and acan, and the expression of COL-II and Aggrecan.	The area and proportion of cartilage and the proportion of new bone were increased, and bone formation was improved.		(135)
	Inflammation	Serum PGRN levels were positively correlated with TNF-α, IL-6, SBP, DBP, BMI, TG, UAER and BMI, and negatively correlated with EGFR	Serum PGRN is closely related to the occurrence of diabetic microangiopathy by promoting Inflammation response.	DN	(140, 141)
	autophagy	PGRN defect: Caspase-3, complex IV and COXIV decreased. The recombinant PGRN activated SIRT1, up-regulated PINK1 and PARK2, inhibited HG induced mitochondrial division, reduced the decline rate of MMP and mtDNA:nDNA, reduced the acetylation of PGC-1α and FoxO1, and enhanced the protein expression of PGC-1α and TFAM. PGRN increased the cleavage of Caspase-3 and PARP1 and the proportion of LC3II/I by mediating CaMKK to activate AMPK, inhibited mTORC1 activity, increased p-ULK1 ser555 site and decreased p-ULK1ser757 site in podocytes.	Promote podocyte mitochondrial homeostasis, induce podocyte autophagy, reduce cell apoptosis, improve podocyte injury in DN mice, and protect renal function.		(142, 143)