Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of murine db/db diabetic kidney to identify adipose differentiation-related protein and regulators of lipid homeostasis.

ABSTRACT: RNA of Kidney was extracted using a Quiagen RNeasy kit. Targets were produced using standard Affymetrix procedures from about 8ug of total RNA.

ORGANISM(S): Mus musculus

DISEASE(S): non-diabetic

SUBMITTER: Michael Simonson

PROVIDER: E-GEOD-642 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Adipose differentiation-related protein and regulators of lipid homeostasis identified by gene expression profiling in the murine db/db diabetic kidney.

Mishra Rangnath R Emancipator Steven N SN Miller Casey C Kern Timothy T Simonson Michael S MS

American journal of physiology. Renal physiology 20040113 5

We investigated the molecular basis of progressive diabetic renal injury in db/db mice by profiling kidney gene expression. Using high-density microarrays, we identified 482 RNA transcripts differentially expressed in 8-wk db/db vs. nondiabetic db/m kidneys, a time characterized by hyperglycemia but by little renal histopathology. By 16 wk significant mesangial expansion had developed. Sixteen-week db/db kidneys differentially expressed 639 RNA transcripts. Diabetic kidneys specifically expresse ...[more]

PMID: 15075187

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Project description:BACKGROUND:Diabetic polyneuropathy (DPN) is the most common and early developing complication of diabetes mellitus, and the key contributor for foot ulcers development, with no specific therapies available. Different studies have shown that mesenchymal stem cell (MSC) administration is able to ameliorate DPN; however, limited cell survival and safety reasons hinder its transfer from bench to bedside. MSCs secrete a broad range of antioxidant, neuroprotective, angiogenic, and immunomodulatory factors (known as conditioned medium), which are all decreased in the peripheral nerves of diabetic patients. Furthermore, the abundance of these factors can be boosted in vitro by incubating MSCs with a preconditioning stimulus, enhancing their therapeutic efficacy. We hypothesize that systemic administration of conditioned medium derived from preconditioned MSCs could reverse DPN and prevent foot ulcer formation in a mouse model of type II diabetes mellitus. METHODS:Diabetic BKS db/db mice were treated with systemic administration of conditioned medium derived from preconditioned human MSCs; conditioned medium derived from non-preconditioned MSCs or vehicle after behavioral signs of DPN was already present. Conditioned medium or vehicle administration was repeated every 2 weeks for a total of four administrations, and several functional and structural parameters characteristic of DPN were evaluated. Finally, a wound was made in the dorsal surface of both feet, and the kinetics of wound closure, re-epithelialization, angiogenesis, and cell proliferation were evaluated. RESULTS:Our molecular, electrophysiological, and histological analysis demonstrated that the administration of conditioned medium derived from non-preconditioned MSCs or from preconditioned MSCs to diabetic BKS db/db mice strongly reverts the established DPN, improving thermal and mechanical sensitivity, restoring intraepidermal nerve fiber density, reducing neuron and Schwann cell apoptosis, improving angiogenesis, and reducing chronic inflammation of peripheral nerves. Furthermore, DPN reversion induced by conditioned medium administration enhances the wound healing process by accelerating wound closure, improving the re-epithelialization of the injured skin and increasing blood vessels in the wound bed in a skin injury model that mimics a foot ulcer. CONCLUSIONS:Studies conducted indicate that MSC-conditioned medium administration could be a novel cell-free therapeutic approach to reverse the initial stages of DPN, avoiding the risk of lower limb amputation triggered by foot ulcer formation and accelerating the wound healing process in case it occurs.

Dataset Information

Transcription profiling of murine db/db diabetic kidney to identify adipose differentiation-related protein and regulators of lipid homeostasis.

Publications

Adipose differentiation-related protein and regulators of lipid homeostasis identified by gene expression profiling in the murine db/db diabetic kidney.

Similar Datasets

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