MicroRNAs are endogenous noncoding RNA molecules with 19-22 nucleotides in length. MicroRNAs can post-transcriptionally regulate gene and (or) protein expression by binding to their target messenger RNAs (mRNAs), leading to mRNA degradation or suppression of translation. As a huge family that regulates gene expression, microRNAs has recently been shown to not only participate in the normal healing processes of wounds but also closely related to pathologic wound healing, and formation of hypertrophic scars and keloids. This review focuses on the biogenesis of microRNA and its role in wound healing.
Animals ; Humans ; MicroRNAs ; Wound Healing ; genetics

Human epidermal growth factor (hEGF) is a typical member of the growth factor family that activates epidermal growth factor receptors. It is synthesized and secreted by multiple tissues and organs of the human body, regulating the cell proliferation, differentiation and migration via binding to receptors and activating a series of signaling pathways. In recent years, the research on hEGF has been extended to its role in human physiology and pathology, especially in tissue regeneration and wound healing. This paper reviews the research progress of hEGF, briefly describes its gene and protein structure and characteristics, mechanisms and biological effects, with the emphasis on the roles and influences in the healing of gastrointestinal ulcers, skin wound repair and tumor pathology.
Cell Proliferation ; Epidermal Growth Factor/genetics* ; ErbB Receptors/genetics* ; Humans ; Skin ; Wound Healing

Alternative Splicing ; Fibronectins/genetics* ; Forensic Medicine ; Humans ; Protein Conformation ; Protein Isoforms/genetics* ; Wound Healing/physiology*

Wound healing, as one of the important public health issues, has been a worldwide problem. Due to the unique biological wound environment, wound healing is a very complex process with current treatments requiring long cycles, being poorly effective, and bringing high economic burden to patients. An increasing number of studies have shown that non-coding RNAs (ncRNAs) play important roles in wound healing process. The competing endogenous RNAs (ceRNAs) hypothesis in recent years is a new proposal on the inter-regulation of RNAs, which suggests a "mode of communication" between different RNAs. ceRNA regulatory network (ceRNET) combines the functions of protein-coding mRNA with ncRNA (e.g., microRNA, long non-coding RNA, pseudogenes, and circular RNA). Recent studies have shown that ceRNAs play important roles in wound healing, which may provide new effective therapeutic targets for wound healing. This paper starting with ceRNET systematically reviewed the research progress on the effects of various ceRNAs in wound healing and the future research challenges, with the aim to deeply explore the molecular mechanisms and clinical significance of ceRNAs in the process of wound healing.
Gene Regulatory Networks ; Humans ; MicroRNAs/genetics* ; RNA, Circular ; RNA, Long Noncoding ; Wound Healing/genetics*

Diabetic wounds are a common complication of diabetic patients, and the incidence has been increasing in recent years. In addition, its poor clinical prognosis seriously affects the quality of life of patients, which has become the focus and difficulty of diabetes treatment. As the RNA regulating gene expression, non-coding RNA can regulate the pathophysiological process of diseases, and play an important role in the healing process of diabetic wounds. In this paper, we reviewed the regulatory role, diagnostic value, and therapeutic potential of three common non-coding RNA in diabetic wounds, in order to provide a new solution for the diagnosis and treatment of diabetic wounds at the genetic and molecular level.
Humans ; Quality of Life ; Diabetes Mellitus/genetics* ; Wound Healing ; RNA, Untranslated/genetics*

Wound age estimation is one of the major tasks in forensic practice. However, relatively accurate estimation of the wound age is still a conundrum and research spotlight world-widely. Studies show that microRNAs (miRNAs) are involved in the whole process of the skin wound repair, and miRNAs, as biomarkers, might be used to estimate the time of skin injury owing to their characteristic advantage. This paper summarizes the miRNA fundamental function, properties, current research progress in the estimation of wound age, and its limitations, and put forward prospect of potential application and research based on miRNAs in estimation of wound age.
Biomarkers ; Humans ; MicroRNAs/genetics* ; Skin/injuries* ; Soft Tissue Injuries ; Wound Healing

Chronological aging is the leading risk factor for human diseases, while aging at the cellular level, namely cellular senescence, is the fundamental driving force of organismal aging. The impact of cellular senescence on various life processes, including normal physiology, organismal aging and the progress of various age-related pathologies, has been largely ignored for a long time. However, with recent advancement in relevant fields, cellular senescence has become the core of aging biology and geriatric medicine. Although senescent cells play important roles in physiological processes including tissue repair, wound healing, and embryonic development, they can also contribute to tissue dysfunction, organ degeneration and various pathological conditions during adulthood. Senescent cells exert paracrine effects on neighboring cells in tissue microenvironments by developing a senescence-associated secretory phenotype, thus maintaining long-term and active intercellular communications that ultimately results in multiple pathophysiological effects. This is regarded as one of the most important discoveries in life science of this century. Notably, selective elimination of senescent cells through inducing their apoptosis or specifically inhibiting the senescence-associated secretory phenotype has shown remarkable potential in preclinical and clinical interventions of aging and age-related diseases. This reinforces the belief that senescent cells are the key drug target to alleviate various aging syndromes. However, senescent cells exhibit heterogeneity in terms of form, function and tissue distribution, and even differ among species, which presents a challenge for the translation of significant research achievements to clinical practice in future. This article reviews and discusses the characteristics of senescent cells, current targeting strategies and future trends, providing useful and valuable references for the rapidly blooming aging biology and geriatric medicine.
Humans ; Adult ; Aged ; Cellular Senescence/genetics* ; Aging ; Apoptosis ; Cell Communication ; Wound Healing/physiology*

OBJECTIVE: In order to supply an effective reference of early injury time estimation and explore the time limit of detection of EDA\EDB mRNA in human skin samples, the expression of alternative splicing segment of fibronectin--EDA\EDB in incised wound of human skin were studied. METHODS: Using in situ hybridization with DIG-labeled anti-sense RNA probe, the expression of FN EDA\EDB domain was detected in human skin incised wound at the early stage of injury (from 30 min to 3 h). RESULTS: The positive expression rates of FN-EDA\EDB immediately after injury and area far away from wound were same as the control group. The expression of FN-EDA\EDB in human skin incised wound showed a gradually increased tendency in early injury time (within 3 h). The positive expression cells were mainly distributed in basement cells of epidermis and the expression of EDA is much higher than EDB. It's difficult to detect EDA\EDB mRNA when the samples were deposited in air for 4 hour. CONCLUSION FN-EDA\EDB may be used as a sensitive mark for the estimation of early injury time. The in-situ hybridization technique is not applicable in the application.
Fibronectins/genetics* ; Forensic Medicine ; Humans ; In Situ Hybridization ; Protein Isoforms/genetics* ; RNA, Messenger/genetics* ; Skin/metabolism* ; Time Factors ; Wound Healing/physiology*

OBJECTIVESTo observe the expression of betaig-h3 in normal cornea and keratoconus and to elucidate the role of extracellular matrix in keratoconus.

METHODSIn situ hybridization was used to detect the expression of betaig-h3 in the cornea. The cDNA library was screened with human betaig-h3 cDNA probe to locate betaig-h3 mRNA in cells.

RESULTSExpression of betaig-h3 was found mainly in the stroma of the normal cornea and keratoconus, but decrease depending on the degree of keratopathy. In some serious cases, no expression signal was detected. The strongest expression was seen at the border of the normal region and keratoconus.

CONCLUSIONSbetaig-h3, the structural component of the extracellular matrix, can affect cell adhensiveness in the development of corneal fibrous interstitial organization. During the development of keratoconus, decreasing levels of betaig-h3 cause the diminution of corneal steadiness, which is related to formation of keratoconus.

Cornea ; metabolism ; Extracellular Matrix Proteins ; Humans ; Keratoconus ; metabolism ; Neoplasm Proteins ; genetics ; RNA, Messenger ; analysis ; Transforming Growth Factor beta ; Wound Healing

OBJECTIVEThis study was undertaken to observe the change in the local level of angiotensin II (Ang II) and the expression of its corresponding receptors AT1 and AT2 during wound healing, and explore the possible role of Ang II in wound healing .

METHODSA model of full-thickness cutaneous wound was developed on the back of C57/BL6 mice. Specimens were taken from the wound of each mouse on the day 0, 1, 3, 5, 7, 9, 11, 13 and 15 after wounding. The change in the generation of Ang II in wounded tissue during the healing process was detected with ELISA. The proliferation and the apoptosis of cells were detected by bromodeoxyuridine (Brdu) and terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling (TUNEL) method in wounded skin during the healing process, respectively. The cellular localization and the mRNA level change of Ang II receptors in wounded tissue during healing were detected with immunostaining and RT-PCR.

RESULTSAng II produced in wounded skin was increased in the first 7 days to reach the peak, and then gradually decreased during wound healing. BrdU labeling index was increased gradually in the first 7 days to reach the peak, and then gradually decreased during wound healing. The number of TUNEL-positive cells was increased slowly in the first 7 days after wounding. The increase in the number of TUNEL-positive cells was more markedly after epithelization of the wound. In normal mice, AT1 and AT2 receptor were found positively expressed in the whole epidermal layer, while positive expression was only found in the endothelial cells of the capillary vessels within the dermal layer, and positive expression was also found in appendages of the skin, i. e. hair follicle, sweat gland and sebaceous gland respectively. Positive staining signal of both AT1 and AT2 receptors were increased in the first 7 days to reach the peak, then gradually decreased. Expression of AT2R was increased again following the epithelization of wound. The result of RT-PCR showed that the expression of both AT1 and AT2 receptors was detectable, and AT1 receptor was increased in the first 7 days to the peak, and then gradually decreased during wound healing, while AT2 receptor expression reached its peak value on day 7, then gradually decreased, and increased again following the epithelization of wound.

CONCLUSIONSThese results indicate that Ang II participate in wound repair and related to remolding in the late stage of wound healing through the change in production of angiotensin II and expression of AT1 and AT2 receptors. AT1 receptor might be closely associated with cell proliferation, while AT2 receptor might play a role in cell apoptosis and remolding during wound healing.

Angiotensin II ; genetics ; metabolism ; Animals ; Apoptosis ; Cell Proliferation ; Male ; Mice ; Mice, Inbred C57BL ; RNA, Messenger ; genetics ; Receptors, Angiotensin ; genetics ; metabolism ; Skin ; injuries ; metabolism ; pathology ; Wound Healing ; physiology