Novel Interactions between TGF-β1 Actions and the 12/15-Lipoxygenase Pathway in Mesangial Cells

Kim, Young-Sook; Xu, Zhenhe; Reddy, Marpadga A.; Li, Shulian; Lanting, Linda; Sharma, Kumar; Adler, Sharon G.; Natarajan, Rama

doi:10.1681/asn.2004070568

Cited by 61 publications

(67 citation statements)

References 50 publications

(68 reference statements)

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“…We previously reported that 12/15-LO and its products can increase TGF-␤1 expression and signaling in MC and vice versa. 17 Taken together with our present observations, it appears that 12/15-LO can crosstalk and amplify the effects of two key potent profibrotic and renal dysfunction-induced agents, TGF-␤1 and Ang II.…”

Section: ( S ) -H E T E 1 2 ( S ) -H E T E + a N G IIsupporting

confidence: 84%

“…[17][18][19][20] Furthermore, cellular growth, matrix production, activation of oxidant stress, specific signaling pathways, and transcriptional factors were attenuated in MMC derived from 12/15-LOKO mice relative to wild type. 20 Importantly, the growth-promoting and matrixinducing effects of Ang II in MC were blocked by 12-LO inhibitors and were also attenuated in MMC derived from 12/15-LOKO mice.…”

Section: Discussionmentioning

confidence: 99%

“…RMC were transfected with empty vector or vector expressing U6 promoter-driven rat 12/15-LO shRNA or scrambled shRNA as described. 17,29 The 12/15-LO shRNA effectively reduced 12/ 15-LO protein expression ( Figure 4A). Furthermore, AT1R protein expression was also significantly reduced in 12/15-LO shRNA-treated MC compared with scrambled control ( Figure 4, A and B).…”

Section: At1r Expression Is Lower In 12/15-lo-deficient MCmentioning

confidence: 97%

“…[17][18][19][20] 12(S)-HETE is involved in multiple events related to the development of these diseases with potency similar to the biofunction of Ang II, 14,17,19 -22 Crossbreeding 12/15-LOKO mice with atherosclerosis-prone ApoE Ϫ/Ϫ mice greatly reduced atherosclerosis development. 12 Our data presented here suggest a close relationship between 12/15-LO and AT1R upregulation.…”

Section: ( S ) -H E T E 1 2 ( S ) -H E T E + a N G IImentioning

confidence: 99%

“…[12][13][14] 12/15-LO is involved in multiple events related to the development of renal disease and DN with potency similar to that of Ang II. [15][16][17][18][19][20] We previously showed that Ang II can induce the activity and expression of 12/15-LO in vascular smooth muscle cells (VSMC) and MC. 19,[21][22][23] The growth-promoting and matrix-inducing effects of Ang II in MC were blocked with pharmacologic 12-LO inhibitors and 12-LO ribozymes.…”

mentioning

confidence: 99%

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Products of 12/15-Lipoxygenase Upregulate the Angiotensin II Receptor

Xu¹,

Yuan²,

Lanting³

et al. 2008

Journal of the American Society of Nephrology

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Angiotensin II and its type 1 receptor (AT1R) play important roles in the pathogenesis of renal disease and diabetic nephropathy. The 12/15-lipoxygenase pathway of arachidonate metabolism and its lipid products have also been implicated in diabetic nephropathy. However, it is unclear whether 12/15-lipoxygenase regulates expression of AT1R. In cultured rat mesangial cells, we found that the 12/15-lipoxygenase product 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) increased AT1R mRNA and protein expression, primarily by stabilizing AT1R mRNA. Pretreatment with 12(S)-HETE also amplified the signaling effects of angiotensin II, likely due to the increased AT1R expression. Levels of AT1R protein expression decreased when 12/15-lipoxygenase was knocked down with specific short hairpin RNA (shRNA) compared with control cells. Similarly, levels of the AT1 receptor, but not the AT2 receptor, were significantly lower in mesangial cells and glomeruli derived from 12/15-lipoxygenase knockout mice compared with control mice. Reciprocally, stable overexpression of 12/15-lipoxygenase increased AT1R expression in cultured mesangial cells. In vivo, modified siRNA targeting 12/15-lipoxygenase reduced glomerular AT1R expression in a diabetic mouse model. Interestingly, angiotensin II induced greater levels of 12/15-lipoxygenase, TGF-␤1, and fibronectin (FN) in AT1R-overexpressing mesangial cells compared with control cells. Therefore, oxidized lipids generated by the 12/15-lipoxygenase-mediated metabolism of arachidonic acid can enhance AT1R expression in mesangial cells and augment the profibrotic effects of angiotensin II.

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Section: ( S ) -H E T E 1 2 ( S ) -H E T E + a N G IIsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: At1r Expression Is Lower In 12/15-lo-deficient MCmentioning

confidence: 97%

Section: ( S ) -H E T E 1 2 ( S ) -H E T E + a N G IImentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Products of 12/15-Lipoxygenase Upregulate the Angiotensin II Receptor

Xu¹,

Yuan²,

Lanting³

et al. 2008

Journal of the American Society of Nephrology

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Cytochrome P450 and Lipoxygenase Metabolites on Renal Function

Imig

Khan

2015

Comprehensive Physiology

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Arachidonic acid metabolites have a myriad of biological actions including effects on the kidney to alter renal hemodynamics and tubular transport processes. Cyclooxygenase metabolites are products of an arachidonic acid enzymatic pathway that has been extensively studied in regards to renal function. Two lesser-known enzymatic pathways of arachidonic acid metabolism are the lipoxygenase (LO) and cytochrome P450 (CYP) pathways. The importance of LO and CYP metabolites to renal hemodynamics and tubular transport processes is now being recognized. LO and CYP metabolites have actions to alter renal blood flow and glomerular filtration rate. Proximal and distal tubular sodium transport and fluid and electrolyte homeostasis are also significantly influenced by renal CYP and LO levels. Metabolites of the LO and CYP pathways also have renal actions that influence renal inflammation, proliferation, and apoptotic processes at vascular and epithelial cells. These renal LO and CYP pathway actions occur through generation of specific metabolites and cell-signaling mechanisms. Even though the renal physiological importance and actions for LO and CYP metabolites are readily apparent, major gaps remain in our understanding of these lipid mediators to renal function. Future studies will be needed to fill these major gaps regarding LO and CYP metabolites on renal function.

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Photothermal lipolysis accelerates ECM production via macrophage‐derived ALOX15‐mediated p38 MAPK activation in fibroblasts

Wang

Yao

et al. 2022

Journal of Biophotonics

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Skin and subcutaneous tissue tightening is usually treated by noninvasive photothermal treatment for medical esthetics purpose, while the underlying mechanism remains to be elucidated. Here, we hypothesized that adipocyte injury, as a stimulator, may regulate extracellular matrix (ECM) production by increasing ALOX15 in macrophages, which could lead to fibroblast activation. In this study, we show that lipolysis was induced by laser heating (45°C for 15 min) in patients and rats, and adipocyte thermal injury stimulates the ECM production in fibroblasts by ALOX15 that was increased in cocultured macrophages. These phenomena were evidenced by the ALOX15 knockdown. In addition, ALOX15 metabolite 12(S)‐HETE activated p38 MAPK signaling pathway that mediated the production of ECM in fibroblast. In summary, the results of this study demonstrate that the mechanisms of adipose photothermal injury‐induced skin and/or subcutaneous tissue tightening may have clinical relevance for noninvasive or minimally invasive photothermal therapeutics.

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Novel Interactions between TGF-β1 Actions and the 12/15-Lipoxygenase Pathway in Mesangial Cells

Abstract: Diabetic nephropathy (DN) is characterized by mesangial cell (MC) hypertrophy and progressive accumulation of glomerular extracellular matrix (ECM).

Cited by 61 publications

References 50 publications

Products of 12/15-Lipoxygenase Upregulate the Angiotensin II Receptor

Products of 12/15-Lipoxygenase Upregulate the Angiotensin II Receptor

Cytochrome P450 and Lipoxygenase Metabolites on Renal Function

Photothermal lipolysis accelerates ECM production via macrophage‐derived ALOX15‐mediated p38 MAPK activation in fibroblasts

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