LncRNA TRHDE-AS1 inhibit the scar fibroblasts proliferation via miR-181a-5p/PTEN axis

AbstractHypertrophic scar (HS), a fibroproliferative disorder caused by abnormal wound healing after skin injury, which is characterized by excessive deposition of extracellular matrix and invasive growth of fibroblasts. Recent studies have shown that some non-coding RNA implicated the formation of HS, but the mechanism remains unclear. In this study, we found that lncRNA TRHDE-AS1 was downregulated in HS tissues and HSFs, and the level of lncRNA TRHDE-AS1 negatively correlated with the level of miR-181a-5p in HS tissue and HSFs. Overexpressed lncRNA TRHDE-AS1 significantly suppressed miR-181a-5p level, while promoted HSFs apoptosis and inhibited HSFs proliferation. Further study shown that PTEN was a direct target of miR-181a-5p, and lncRNA TRHDE-AS1 served as a molecular sponge for miR-181a-5p to regulate the expression of PTEN. Overexpression of PTEN could eliminate lncRNA TRHDE-AS1-mediated proliferation suppression of HSFs. In conclusion, our study suggested that lncRNA TRHDE-AS1/miR-181a-5p/PTEN axis plays an important role in promoting hypertrophic scar formation, which may be effectively used as a therapeutic target for hypertrophic scar treatment.

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Therapeutic Strategies by Regulating Interleukin Family to Suppress Inflammation in Hypertrophic Scar and Keloid

Frontiers in Pharmacology ◽

10.3389/fphar.2021.667763 ◽

2021 ◽

Vol 12 ◽

Author(s):

Dan Zhang ◽

Bo Li ◽

Muxin Zhao

Keyword(s):

Wound Healing ◽

Immune Responses ◽

Psychological Stress ◽

Therapeutic Target ◽

Hypertrophic Scar ◽

Critical Role ◽

Therapeutic Strategies ◽

Scar Formation ◽

Clinical Treatment ◽

Keloid Formation

Hypertrophic scar (HS) and keloid are fibroproliferative disorders (FPDs) of the skin due to aberrant wound healing, which cause disfigured appearance, discomfort, dysfunction, psychological stress, and patient frustration. The unclear pathogenesis behind HS and keloid is partially responsible for the clinical treatment stagnancy. However, there are now increasing evidences suggesting that inflammation is the initiator of HS and keloid formation. Interleukins are known to participate in inflammatory and immune responses, and play a critical role in wound healing and scar formation. In this review, we summarize the function of related interleukins, and focus on their potentials as the therapeutic target for the treatment of HS and keloid.

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Hypertrophic scar formation after skin injury

Journal of Wound Care ◽

10.12968/jowc.1993.2.5.299 ◽

1993 ◽

Vol 2 (5) ◽

pp. 299-302 ◽

Cited By ~ 10

Author(s):

S. A. Carney

Keyword(s):

Hypertrophic Scar ◽

Scar Formation ◽

Skin Injury

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The Long Non-Coding RNA LncRNA8975-1 is Upregulated in Hypertrophic Scar Fibroblasts and Controls Collagen Expression

Cellular Physiology and Biochemistry ◽

10.1159/000452548 ◽

2016 ◽

Vol 40 (1-2) ◽

pp. 326-334 ◽

Cited By ~ 14

Author(s):

Jun Li ◽

Ling Chen ◽

Chunyu Cao ◽

Hui Yan ◽

Bei Zhou ◽

...

Keyword(s):

Cell Proliferation ◽

Hypertrophic Scar ◽

Smooth Muscle Actin ◽

Scar Formation ◽

Dermal Fibroblasts ◽

Alpha Smooth Muscle Actin ◽

Protein Levels ◽

Reverse Transcription Pcr ◽

Non Coding Rna ◽

Long Non Coding Rna

Background/Aims: Long non-coding RNAs (lncRNAs) are thought to play crucial roles in human diseases. However, the function of lncRNAs in hypertrophic scar formation remains poorly understood. Methods: In this study, we investigated the expression of lncRNA8975-1 in hypertrophic scar tissues and fibroblasts by quantitative reverse transcription PCR (qRT-PCR). To investigate its function, overexpression and knockdown of lncRNA8975-1 were performed using lentivirus infection and Stealth RNAi transfection, respectively. Cell proliferation was detected by CCK-8 assay. The protein levels of collagens and alpha-smooth muscle actin (α-SMA) were analysed by western blot. Results: We found that lncRNA8975-1 was overexpressed in hypertrophic scar tissues and dermal fibroblasts. Overexpression of lncRNA8975-1 inhibited cell proliferation and reduced the protein expression levels of COL1A2, COL1A1, COL3A1 and α-SMA in hypertrophic scar fibroblasts, whereas knockdown of lncRNA8975-1 had the opposite effect. Conclusion: Our results show that the long non-coding RNA lncRNA8975-1 is upregulated in hypertrophic scar fibroblasts; furthermore, it inhibits fibroblast proliferation and reduces collagen and α-SMA expression. Further studies on the mechanisms regulated by lncRNA8975-1 would lead to a better understanding of the pathogenesis of hypertrophic scar formation.

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The Temporal Effects of Anti-TGF-β1, 2, and 3 Monoclonal Antibody on Wound Healing and Hypertrophic Scar Formation

Journal of the American College of Surgeons ◽

10.1016/j.jamcollsurg.2005.03.032 ◽

2005 ◽

Vol 201 (3) ◽

pp. 391-397 ◽

Cited By ~ 122

Author(s):

Leonard Lu ◽

Alexandrina S. Saulis ◽

W. Robert Liu ◽

Nakshatra K. Roy ◽

Jerome D. Chao ◽

...

Keyword(s):

Monoclonal Antibody ◽

Wound Healing ◽

Hypertrophic Scar ◽

Scar Formation ◽

Temporal Effects ◽

Tgf Β1

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The extracellular matrix of lip wounds in fetal, neonatal and adult mice

Development ◽

10.1242/dev.112.2.651 ◽

1991 ◽

Vol 112 (2) ◽

pp. 651-668

Author(s):

D.J. Whitby ◽

M.W. Ferguson

Keyword(s):

Extracellular Matrix ◽

Wound Healing ◽

Cell Migration ◽

Inflammatory Response ◽

Cell Function ◽

Chondroitin Sulphate ◽

Scar Formation ◽

Collagen Types ◽

Cellular Mechanisms ◽

Collagen Formation

Wound healing in the fetus occurs rapidly, by a regenerative process and without an inflammatory response, resulting in complete restitution of normal tissue function. By contrast, in the adult, wounds heal with scar formation, which may impair function and inhibit further growth. The cellular mechanisms underlying these differing forms of wound healing are unknown but the extracellular matrix (ECM), through its effects on cell function, may play a key role. We have studied the ECM in upper lip wounds of adult, neonatal and fetal mice at days 14, 16 and 18 of gestation. The spatial and temporal distribution of collagen types I, III, IV, V and VI, fibronectin, tenascin, laminin, chondroitin and heparan sulphates were examined immunohistochemically. Results from the fetal groups were essentially similar whilst there were distinct differences between fetus, neonate and adult. Fibronectin was present at the surface of the wound in all groups at 1 h post-wounding. Tenascin was also present at the wound surface but the time at which it was first present differed between fetus (1 h), neonate (12 h) and adult (24 h). The time of first appearance paralleled the rate of wound healing which was most rapid in the fetus and slowest in the adult. Tenascin inhibits the cell adhesion effect of fibronectin and during development the appearance of tenascin correlates with the initiation of cell migration. During wound healing the appearance of tenascin preceded cell migration and the rapid closure of fetal wounds may be due to the early appearance of tenascin in the wound. Collagen types I, III, IV, V and VI were present in all three wound groups but the timing and pattern of collagen deposition differed, with restoration of the normal collagen pattern in the fetus and a scar pattern in the adult. This confirms that lack of scarring in fetal wounds is due to the organisation of collagen within the wound and not simply lack of collagen formation. The distribution of chondroitin sulphate differed between normal fetal and adult tissues and between fetal and adult wounds. Its presence in the fetal wound may alter collagen fibril formation. No inflammatory response was seen in the fetal wounds. The differences in the ECM of fetal and adult wounds suggests that it may be possible to alter the adult wound so that it heals by a fetal-like process without scar formation, loss of tissue function or restriction of growth.

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Wound Healing Versus Regeneration: Role of the Tissue Environment in Regenerative Medicine

MRS Bulletin ◽

10.1557/mrs2010.528 ◽

2010 ◽

Vol 35 (8) ◽

pp. 597-606 ◽

Cited By ~ 39

Author(s):

Anthony Atala ◽

Darrell J. Irvine ◽

Marsha Moses ◽

Sunil Shaunak

Keyword(s):

Extracellular Matrix ◽

Wound Healing ◽

Regenerative Medicine ◽

Tissue Regeneration ◽

Normal Tissue ◽

Disease Process ◽

Scar Formation ◽

The Body ◽

Mechanistic Basis

AbstractOne of the major challenges in the field of regenerative medicine is how to optimize tissue regeneration in the body by therapeutically manipulating its natural ability to form scar at the time of injury or disease. It is often the balance between tissue regeneration, a process that is activated at the onset of disease, and scar formation, which develops as a result of the disease process that determines the ability of the tissue or organ to be functional. Using biomaterials as scaffolds often can provide a “bridge” for normal tissue edges to regenerate over small distances, usually up to 1 cm. Larger tissue defect gaps typically require both scaffolds and cells for normal tissue regeneration to occur without scar formation. Various strategies can help to modulate the scar response and can potentially enhance tissue regeneration. Understanding the mechanistic basis of such multivariate interactions as the scar microenvironment, the immune system, extracellular matrix, and inflammatory cytokines may enable the design of tissue engineering and wound healing strategies that directly modulate the healing response in a manner favorable to regeneration.

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Understanding the mechanisms that determine extracellular matrix remodeling in the infarcted myocardium

Biochemical Society Transactions ◽

10.1042/bst20190113 ◽

2019 ◽

Vol 47 (6) ◽

pp. 1679-1687

Author(s):

Mavis A.A. Tenkorang ◽

Upendra Chalise ◽

Michael J. Daseke, II ◽

Shelby R. Konfrst ◽

Merry L. Lindsey

Keyword(s):

Myocardial Infarction ◽

Extracellular Matrix ◽

Wound Healing ◽

Inflammatory Response ◽

Current Knowledge ◽

Scar Formation ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling ◽

Ecm Remodeling ◽

Infarcted Myocardium

Myocardial Infarction (MI) initiates a series of wound healing events that begins with up-regulation of an inflammatory response and culminates in scar formation. The extracellular matrix (ECM) is intricately involved in all stages from initial break down of existing ECM to synthesis of new ECM to form the scar. This review will summarize our current knowledge on the processes involved in ECM remodeling after MI and identify the gaps that still need to be filled.

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Systemic depletion of macrophages in the subacute phase of wound healing reduces hypertrophic scar formation

Wound Repair and Regeneration ◽

10.1111/wrr.12442 ◽

2016 ◽

Vol 24 (4) ◽

pp. 644-656 ◽

Cited By ~ 39

Author(s):

Zhensen Zhu ◽

Jie Ding ◽

Zengshuan Ma ◽

Takashi Iwashina ◽

Edward E. Tredget

Keyword(s):

Wound Healing ◽

Hypertrophic Scar ◽

Scar Formation ◽

Subacute Phase

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Regeneration of Dermis: Scarring and Cells Involved

Cells ◽

10.3390/cells8060607 ◽

2019 ◽

Vol 8 (6) ◽

pp. 607 ◽

Cited By ~ 24

Author(s):

Alexandra L. Rippa ◽

Ekaterina P. Kalabusheva ◽

Ekaterina A. Vorotelyak

Keyword(s):

Extracellular Matrix ◽

Wound Healing ◽

Hair Follicle ◽

Scar Formation ◽

Population Characteristics ◽

Matrix Composition ◽

Skin Substitutes ◽

Skin Repair ◽

Dermal Cell

There are many studies on certain skin cell specifications and their contribution to wound healing. In this review, we provide an overview of dermal cell heterogeneity and their participation in skin repair, scar formation, and in the composition of skin substitutes. The papillary, reticular, and hair follicle associated fibroblasts differ not only topographically, but also functionally. Human skin has a number of particular characteristics that are different from murine skin. This should be taken into account in experimental procedures. Dermal cells react differently to skin wounding, remodel the extracellular matrix in their own manner, and convert to myofibroblasts to different extents. Recent studies indicate a special role of papillary fibroblasts in the favorable outcome of wound healing and epithelial-mesenchyme interactions. Neofolliculogenesis can substantially reduce scarring. The role of hair follicle mesenchyme cells in skin repair and possible therapeutic applications is discussed. Participation of dermal cell types in wound healing is described, with the addition of possible mechanisms underlying different outcomes in embryonic and adult tissues in the context of cell population characteristics and extracellular matrix composition and properties. Dermal white adipose tissue involvement in wound healing is also overviewed. Characteristics of myofibroblasts and their activity in scar formation is extensively discussed. Cellular mechanisms of scarring and possible ways for its prevention are highlighted. Data on keloid cells are provided with emphasis on their specific characteristics. We also discuss the contribution of tissue tension to the scar formation as well as the criteria and effectiveness of skin substitutes in skin reconstruction. Special attention is given to the properties of skin substitutes in terms of cell composition and the ability to prevent scarring.

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