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Posttranscriptional control of PLOD1 in adipose-derived stem cells regulates scar formation through altering macrophage polarization.

ABSTRACT:

Background

The level of cutaneous scar formation is a critical parameter to determine the success of skin wound healing. Adipose-derived mesenchymal stem cells (AMSCs) have been applied to improve treatment of cutaneous injury with the purpose of reducing scar formation.

Methods

The levels of procollagen-lysine 1,2-oxoglutarate 5-dioxygenase 1 (PLOD1) were assessed at scar sites. Then, PLOD1 in AMSCs was depleted by either expression of a PLOD1-specific short-hair interfering RNA (shPLOD1) or by expression of microRNA-449 (miR-449) that targets and suppresses protein translation of PLOD1 through 3 prime untranslated region (3'-UTR) interfering. For induction of skin injury, a blade cut of 1.5-cm long and 2-mm thick was made on the middle back of the mice. Transplantation of either AMSCs-shPLOD1 or AMSCs-miR-449 into the injured region of the mice was performed via tail vein injection. The fibrosis as well as underlying mechanisms were assessed.

Results

The AMSCs expressed high levels of PLOD1, a potent stimulator of fibrosis. We knocked down PLOD1 in AMSCs by expression of either shPLOD1 or miR-449. Transplantation of either AMSCs-shPLOD1 or AMSCs-miR-449 significantly reduced the fibrotic process in the injured region of the mice to a similar degree. Mechanistically, transplantation of either AMSCs-shPLOD1 or AMSCs-miR-449 shifted macrophage polarization from M2 to M1-like and reduced both reactive oxygen species (ROS) and activation of myofibroblasts from fibroblasts.

Conclusions

Suppression of PLOD1 levels in AMSCs either directly by shPLOD1 or indirectly by miR-449 may substantially improve the anti-fibrotic potential of AMSCs during wound healing, likely through altering macrophage polarization.

SUBMITTER: Xu M

PROVIDER: S-EPMC8576667 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Posttranscriptional control of <i>PLOD1</i> in adipose-derived stem cells regulates scar formation through altering macrophage polarization.

Xu Miao M Fang Shuo S Xie Aiguo A

Annals of translational medicine 20211001 20

<h4>Background</h4>The level of cutaneous scar formation is a critical parameter to determine the success of skin wound healing. Adipose-derived mesenchymal stem cells (AMSCs) have been applied to improve treatment of cutaneous injury with the purpose of reducing scar formation.<h4>Methods</h4>The levels of procollagen-lysine 1,2-oxoglutarate 5-dioxygenase 1 (<i>PLOD1</i>) were assessed at scar sites. Then, <i>PLOD1</i> in AMSCs was depleted by either expression of a PLOD1-specific short-hair in ...[more]

PMID: 34790779

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