A close relationship between type 1 diabetes and vitamin A-deficiency and matrix metalloproteinase and hyaluronidase activities in skin tissues

Abstract

Numerous wrinkles are observed in the skin of streptozotocin (STZ)-induced type 1 diabetic rats, which are similar to those seen in vitamin A-deficient (VAD) rats. Retinoic acid (RA), the active form of vitamin A, promotes the production of collagen in dermis and induces cell growth and inhibition of epidermal differentiation in skin tissues. Normal skin function is maintained by the extracellular matrix (ECM)-degrading enzymes, matrix metalloproteinase (MMP) and hyaluronidase (HAase). This study is the first comparison of MMP and HAase activities in skin tissues of type 1 diabetic, VAD and RA-treated animal models. In skin tissues of type 1 diabetic and VAD rats or VAD mice, both MMP-2 and HAase activities increased as compared with controls. In contrast, MMP and HAase activities were reduced in the skin tissues of RA-treated mice. Blood retinol levels in type 1 diabetic rats were lower than controls. These results indicate a close relationship between type 1 diabetes and vitamin A-deficiency on MMP and HAase in skin tissues, suggesting that type 1 diabetic rats could be vitamin A-deficient. Vitamin A-derived RA might be a significant regulator of ECM-degrading enzyme expression and diabetic symptoms.

Alteration of the bone tissue material properties in type 1 diabetes mellitus: A Fourier transform infrared microspectroscopy study

“…These modifications cannot be explained by the augmented collagen glycation but rather by enzymatic degradation of matrix collagen. Interestingly, further reports have been made regarding higher matrix metalloproteinase (MMP) activities, mainly MMP-2, MMP-8, MMP-9, MMP-13 and MMP-14, in connective tissues, other than bone, in type 1 diabetes [38][39][40][41][42]. To the best of our knowledge, MMP activities have never been assessed in bone tissue of diabetic animals.…”

Vitamin A Deficiency and Alterations in the Extracellular Matrix

“…Liver, pulmonary and renal fibrosis are common pathological states which represent a major global health problem, and effective therapeutic measures are presently unavailable [ 189 ]. The similarities in the ECM modifications occurring in VAD and in some other diseases, and the reversibility of most VAD-induced alterations by RA, suggest that some degree of VAD might be present in those diseases and underscores the potentially beneficial effects of retinoid treatment [ 109 , 138 , 141 , 168 , 190 , 191 , 192 , 193 , 194 , 195 ]. In fact, RA treatment has proved beneficial in several experimental diseases.…”

The Controversial Role of Retinoic Acid in Fibrotic Diseases: Analysis of Involved Signaling Pathways

“…RA inhibits the expression of TSP [4], TGF-β1 [54], collagen I [54–58], collagen II [59], collagen III [54,58], collagen VII [58], collagen X [59], LN [55,60], α-SMA [55], FN [4,55,56,58,61,62], 5-lipoxygenase (5-LOX) [54], CTGF [54], cysteine-rich protein 61 (CCN1) [63,64], procollagen I [63–65], MMP-1 [63,64,66], MMP-2 [67], and is able to down-regulate the accumulation of ECM. However, several independent studies found that RA could up-regulate the expression of FN [57,59], collagen I [59,60], collagen IV [68,69], TSP [57], LN [57,70], MMP-2 [71], MMP-9 [71], GPRC5B [72], integrin α5 [73], IGF1 [74] and IGF2 [74], which results in the opposite effect as reported above, i.e ., the induction of ECM accumulation [68,75,76].…”