Involvement of miRNA203 in the proliferation of epidermal stem cells during the process of DM chronic wound healing through Wnt signal pathways.
Liu Jian,Shu Bin,Zhou Ziheng,Xu Yingbin,Liu Yiling,Wang Peng,Xiong Kun,Xie Julin
Stem cell research & therapy
BACKGROUND:The biological role of miR-203 and the underlying mechanisms on the proliferation of epidermal stem cells (ESCs) have not yet been reported during the progression of chronic wound healing in diabetes mellitus. Our previous studies have observed that the expression of miR-203 showed a marked upregulation and ESC proliferation capacity was impaired in diabetes mellitus skin wounds in rats. METHODS:Wound models were established in normal rats and rats with type 2 diabetes. Expression level of miR-203 and the alteration of ESCs' number and function were detected. ESCs were isolated from the back skin of fetal rats to assess the effects of glucose in vitro. An antagomir to miR-203 was used to assess its effect on ESCs. Using microarray analysis, we further identified potential target genes and signaling pathways of miR-203. RESULTS:We found that high glucose significantly upregulated the expression of miR-203 and subsequently reduced the number of ESCs and impaired their proliferation capacity. Meanwhile, over-expression of miR-203 reduced the ESCs' numbers and impaired the proliferation capacity via downregulation of the Notch and Wnt signaling pathways. Conversely, inhibition of miR-203 enhanced the proliferation capacity. Additionally, silencing miR-203 in skin of rats with type 2 diabetes accelerated wound healing and improved healing quality via the upregulation of the Notch and Wnt signaling pathways. Finally, over-expression of miR-203 downregulated genes ROCK2, MAPK8, MAPK9, and PRKCA. CONCLUSION:Our findings demonstrated that induced expression of miR-203 by high glucose in type 2 diabetic rats decreased the number of ESCs and impaired ESC proliferation capacity via downregulating genes related to Notch and Wnt signaling pathways, resulting in a delayed wound healing.
Streptozotocin-Induced Diabetic Models in Mice and Rats.
Furman Brian L
Streptozotocin (STZ) is an antibiotic that causes pancreatic islet β-cell destruction and is widely used experimentally to produce a model of type 1 diabetes mellitus (T1DM). Detailed in this article are protocols for producing STZ-induced insulin deficiency and hyperglycemia in mice and rats. Also described are protocols for creating animal models for type 2 diabetes using STZ. These animals are employed for assessing the pathological consequences of diabetes and for screening potential therapies for the treatment of this condition. © 2021 The Authors.
Preclinical models of diabetic wound healing: A critical review.
Sanapalli Bharat Kumar Reddy,Yele Vidyasrilekha,Singh Mantosh Kumar,Thaggikuppe Krishnamurthy Praveen,Karri Veera Venkata Satyanarayana Reddy
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
The treatment of diabetic wounds (DWs) is always challenging for the medical community because of its multifaceted pathophysiology. Due to practical and ethical considerations, direct studies of therapeutic interventions on human subjects are limited. Thus, it is ideal for performing studies on animals having less genetic and biological variability. An ideal DW model should progress toward reproducibility, quantifiable interpretation, therapeutic significance, and effective translation into clinical use. In the last couple of decades, various animal models were developed to examine the complex cellular and biochemical process of skin restoration in DW healing. Also, these models were used to assess the potency of developed active pharmaceutical ingredients and formulations. However, many animal models lack studying mechanisms that can appropriately restate human DW, stay a huge translational challenge. This review discusses the available animal models with their significance in DW experiments and their limitations, focusing on levels of proof of effectiveness in selecting appropriate models to restate the human DW to improve clinical outcomes. Although numerous newer entities and combinatory formulations are very well appreciated preclinically for DW management, they fail in clinical trials, which may be due to improper selection of the appropriate model. The major future challenge could be developing a model that resembles the human DW environment, can potentiate translational research in DW care.