PMID- 33792156
OWN - NLM
STAT- MEDLINE
DCOM- 20211221
LR  - 20231108
IS  - 1742-481X (Electronic)
IS  - 1742-4801 (Print)
IS  - 1742-4801 (Linking)
VI  - 19
IP  - 1
DP  - 2022 Jan
TI  - Pyridoxamine ameliorates methylglyoxal-induced macrophage dysfunction to 
      facilitate tissue repair in diabetic wounds.
PG  - 52-63
LID - 10.1111/iwj.13597 [doi]
AB  - Methylglyoxal (MGO) is a highly reactive dicarbonyl compound formed during 
      hyperglycaemia. MGO combines with proteins to form advanced glycation end 
      products (AGEs), leading to cellular dysfunction and organ damage. In type 2 
      diabetes mellitus (T2DM), the higher the plasma MGO concentration, the higher the 
      lower extremity amputation rate. Here, we aimed to identify the mechanisms of 
      MGO-induced dysfunction. We observed that the accumulation of MGO-derived AGEs in 
      human diabetic wounds increased, whereas the expression of glyoxalase 1 (GLO1), a 
      key metabolic enzyme of MGO, decreased. We show for the first time that topical 
      application of pyridoxamine (PM), a natural vitamin B6 analogue, reduced the 
      accumulation of MGO-derived AGEs in the wound tissue of type-2 diabetic mice, 
      promoted the influx of macrophages in the early stage of tissue repair, improved 
      the dysfunctional inflammatory response, and accelerated wound healing. In vitro, 
      MGO damaged the phagocytic functions of M1-like macrophages induced by 
      lipopolysaccharide (LPS), but not those of M0-like macrophages induced by PMA or 
      of M2-like macrophages induced by interleukins 4 (IL-4) and 13 (IL-13); the 
      impaired phagocytosis of M1-like macrophages was rescued by PM administration. 
      These findings suggest that the increase in MGO metabolism in vivo might 
      contribute to macrophage dysfunction, thereby affecting wound healing. Our 
      results indicate that PM may be a novel therapeutic approach for treating 
      diabetic wounds. MGO forms protein adducts that cause macrophage dysfunction. 
      These adducts cause cell and organ dysfunction that is common in diabetes. 
      Pyridoxamine scavenges MGO to ameliorate this dysfunction, promoting wound 
      healing. Pyridoxamine could be used therapeutically to treat non-healing diabetic 
      wounds.
CI  - (c) 2021 The Authors. International Wound Journal published by Medicalhelplines.com 
      Inc (3M) and John Wiley & Sons Ltd.
FAU - Jiang, Minfei
AU  - Jiang M
AUID- ORCID: 0000-0002-4919-8551
AD  - Department of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Yakupu, Aobuliaximu
AU  - Yakupu A
AD  - Department of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Guan, Haonan
AU  - Guan H
AD  - Department of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Dong, Jiaoyun
AU  - Dong J
AD  - Department of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Liu, Yingkai
AU  - Liu Y
AD  - Department of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Song, Fei
AU  - Song F
AD  - Department of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Tang, Jiajun
AU  - Tang J
AD  - Department of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Tian, Ming
AU  - Tian M
AD  - Department of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Niu, Yiwen
AU  - Niu Y
AUID- ORCID: 0000-0002-5870-3089
AD  - Department of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Lu, Shuliang
AU  - Lu S
AUID- ORCID: 0000-0001-9476-2564
AD  - Department of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
LA  - eng
GR  - 81272111/National Natural Science Foundation of China/
GR  - 81670752/National Natural Science Foundation of China/
GR  - 81671916/National Natural Science Foundation of China/
GR  - 19ZR1432200/Natural Science Foundation of Shanghai/
PT  - Journal Article
DEP - 20210331
PL  - England
TA  - Int Wound J
JT  - International wound journal
JID - 101230907
RN  - 6466NM3W93 (Pyridoxamine)
RN  - 722KLD7415 (Pyruvaldehyde)
SB  - IM
MH  - Animals
MH  - *Diabetes Mellitus, Experimental
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Macrophages
MH  - Mice
MH  - Pyridoxamine/therapeutic use
MH  - Pyruvaldehyde
MH  - Wound Healing
PMC - PMC8684884
OTO - NOTNLM
OT  - advanced glycation end products
OT  - diabetic wound
OT  - macrophage
OT  - methylglyoxal
OT  - pyridoxamine
COIS- The authors have no conflicts of interest to declare.
EDAT- 2021/04/02 06:00
MHDA- 2021/12/22 06:00
PMCR- 2021/03/31
CRDT- 2021/04/01 06:51
PHST- 2021/03/16 00:00 [revised]
PHST- 2021/02/05 00:00 [received]
PHST- 2021/03/23 00:00 [accepted]
PHST- 2021/04/02 06:00 [pubmed]
PHST- 2021/12/22 06:00 [medline]
PHST- 2021/04/01 06:51 [entrez]
PHST- 2021/03/31 00:00 [pmc-release]
AID - IWJ13597 [pii]
AID - 10.1111/iwj.13597 [doi]
PST - ppublish
SO  - Int Wound J. 2022 Jan;19(1):52-63. doi: 10.1111/iwj.13597. Epub 2021 Mar 31.