Activation of skin renin–angiotensin system in diabetic rats

Abstract

The renin-angiotensin system (RAS) is reportedly involved in chronic diabetic complications such as diabetic nephropathy, but changes of the RAS in diabetic skin remain unknown. The aim of this study was to investigate the expression of angiotensin (Ang) II and its type 1 (AT1) and type 2 (AT2) receptors in diabetic skin tissues, and explore the relationship between the local RAS and pathological changes of diabetic skin. Our results showed that thinning of epidermis, degeneration of collagen, fracture of dermal layer, and atrophy/disappearance of subcutaneous fat were observed in diabetic skin. The expression level of AngII was increased in diabetic skin tissues compared to that in controls. mRNA and protein expression of AT1 receptor were also increased while the level of AT2 receptor decreased; the relative expression of AT1 to AT2 receptors was approximately threefold higher in diabetes than in controls. Furthermore, in the culture medium of primary cultured fibroblasts from diabetic skin, the concentration of AngII was significantly higher than that of normal control. The mRNA and protein expression of AT1 receptor was also increased in fibroblasts of diabetic skin compared to controls, while the protein expression of AT2 receptor was decreased. Taken together, our results suggest that the local RAS system is activated in diabetic skin and AngII receptor is likely to mediate the pathological changes of diabetic skin.

Angiotensin II regulates collagen metabolism through modulating tissue inhibitor of metalloproteinase-1 in diabetic skin tissues

“…Our previous study showed that skin tissues synthesised Ang II itself locally, and local expression of Ang II was significantly increased in diabetic skin, which was closely associated with collagen metabolism and ECM production in diabetic skin tissues. 16 Recently, evidence has been presented that defined a role of Ang II in stimulation of collagen gene expression and protein turnover in cultured cardiac fibroblasts. 31,32 Here, our results demonstrated TGF-β activation induced by Ang II, which was in line with other studies that demonstrated Ang II regulated synthesis of TGF-β.…”

“…The thickness of dermis of diabetic skin tissues was significantly thinner, with thin, degenerated and fractured collagen fibres. 16 In this study, we observed the distribution of collagen and calculated the percentages of Coll I and Coll III in skin tissues. When observed in light microscope, the collagen demonstrated red colour (Figure 1(a) and (b)).…”

“…12,13 Angiotensin II (Ang II) affects proliferation, apoptosis, migration, collagen metabolism and capillary formation of skin cells via its receptors. 14,15 Our previous study has suggested that Ang II and its functional receptors were significantly increased in diabetic skin fibroblasts, 16 indicating that the upregulation of Ang II type 1 (AT1) receptor might influence diabetic fibroblast functions related to ECM remodelling. Previous reports also suggested the role of Ang II in MMP and TIMP system regulation through a TGF-β-dependent mechanism in some cell lines, including proximal tubule cells; 17 however, the effect of Ang II on MMP-1/TIMP-1 balance in collagen metabolism of diabetic skin remains unknown.…”

Chronic wound repair and healing in older adults: Current status and future research

“…With diabetes or age, skin shows increased expression of angiotensin II and the proinflammatory, vasoconstrictive angiotensin 1 receptor signaling pathway. [48][49][50] Treatment with the angiotensin receptor blocker (ARB) losartan improves muscle remodeling after injury, 51 and diabetic individuals taking ARBs are less likely to undergo amputation, compared with those taking angiotensin-converting enzyme inhibitors. 52 Thus, angiotensin receptor signaling likely increases fibrosis and satellite cell deactivation and may serve as a target for wound healing.…”

Chronic Wound Repair and Healing in Older Adults: Current Status and Future Research

“…Angiotensin receptor signaling influences TGF‐β expression. With diabetes mellitus or age, skin has greater expression of angiotensin II and the proinflammatory, vasoconstrictive AT1 receptor‐signaling pathway . Treatment with the angiotensin receptor blocker (ARB) losartan improves muscle remodeling after injury, and individuals with diabetes mellitus taking ARBs are less likely to undergo amputation than those taking angiotensin‐converting enzyme inhibitors, indicating that angiotensin receptor signaling increases fibrosis and satellite cell deactivation and may serve as a target for wound healing.…”