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Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions

Low oxygen levels (hypoxia) trigger a variety of adaptive responses with the Hypoxia-inducible factor 1 (HIF-1) complex acting as a master regulator. ...

Karolinska University Hospital

Hypoxia plays a major pathogenic role in diabetic nephropathy (DN). We have investigated in this study the effect of hypoxia-inducible factor 1 α subunit (HIF1A) genetic polymorphisms on the development of DN.

Impact of the hypoxia-inducible factor-1 α (HIF1A) Pro582Ser polymorphism on diabetes nephropathy.

Selective blockade of estrogen receptor beta improves wound healing in diabetes.

Chronic wounds represent a major and rising health and economic burden worldwide. There is a continued search toward more effective wound therapy. We found significantly reduced microRNA-132 (miR-132) expression in human diabetic ulcers compared with normal skin wounds and also in skin wounds of leptin receptor-deficient (db/db) diabetic mice compared with wild-type mice. Local replenishment of miR-132 in the wounds of db/db mice accelerated wound closure effectively, which was accompanied by increased proliferation of wound edge keratinocytes and reduced inflammation. The pro-healing effect of miR-132 was further supported by global transcriptome analysis, which showed that several inflammation-related signaling pathways (e.g., NF-κB, NOD-like receptor, toll-like receptor, and tumor necrosis factor signaling pathways) were the top ones regulated by miR-132 in vivo. Moreover, we topically applied liposome-formulated miR-132 mimics mixed with pluronic F-127 gel on human ex vivo skin wounds, which promoted re-epithelialization. Together, our study showed the therapeutic potential of miR-132 in chronic wounds, which warrants further evaluation in controlled clinical trials.

MicroRNA-132 with Therapeutic Potential in Chronic Wounds.

IGF-I is a growth factor, which is expressed in virtually all tissues. The circulating IGF-I is however derived mainly from the liver. IGF-I promotes wound healing and its levels are decreased in wounds with low regenerative potential such as diabetic wounds. However, the contribution of circulating IGF-I to wound healing is unknown. Here we investigated the role of systemic IGF-I on wound healing rate in mice with deficiency of liver-derived IGF-I (LI-IGF-I-/- mice) during normal (normoglycemic) and impaired wound healing (diabetes).

Article	Year
Impact of the hypoxia-inducible factor-1 α (HIF1A) Pro582Ser polymorphism on diabetes nephropathy. Diabetes care\| PubMed ID: 22991450	2013
Selective blockade of estrogen receptor beta improves wound healing in diabetes. Endocrine\| PubMed ID: 24366647	2014
MicroRNA-132 with Therapeutic Potential in Chronic Wounds. The Journal of investigative dermatology\| PubMed ID: 28807666	2017
Deficiency of liver-derived insulin-like growth factor-I (IGF-I) does not interfere with the skin wound healing rate. PloS one\| PubMed ID: 29534073	2018

Xiaowei Zheng

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