Histochemical and cellular changes accompanying the appearance of lung fibrosis in an experimental mouse model for Hermansky Pudlak syndrome

Wang, Lingyan; Lyerla, Timothy A.

doi:10.1007/s00418-010-0724-8

Cited by 23 publications

(17 citation statements)

References 24 publications

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“…48 Immunohistochemical staining was performed on 4-mm kidney sections as previously described. 48 Briefly, the kidney sections were stained by anti-a-SMA (Sigma-Aldrich), anticollagen I (Calbiochem, San Diego, CA), antifibronectin (Sigma-Aldrich), anti-CD4 (Santa Cruz Biotechnology, Santa Cruz, CA), and anti-CD8 (Santa Cruz Biotechnology) antibody, respectively, and then detected by the EnVision/ HRP Kit (Dako, Carpinteria, CA). …”

Section: Morphologic and Immunohistochemical Analysesmentioning

confidence: 99%

Retraction: GQ5 Hinders Renal Fibrosis in Obstructive Nephropathy by Selectively Inhibiting TGF-β–Induced Smad3 Phosphorylation

Nie

et al. 2015

Journal of the American Society of Nephrology

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TGF-b1, via Smad-dependent or Smad-independent signaling, has a central role in the pathogenesis of renal fibrosis. This pathway has been recognized as a potential target for antifibrotic therapy. Here, we identified GQ5, a small molecular phenolic compound isolated from the dried resin of Toxicodendron vernicifluum, as a potent and selective inhibitor of TGF-b1-induced Smad3 phosphorylation. In TGF-b1-stimulated renal tubular epithelial cells and interstitial fibroblast cells, GQ5 inhibited the interaction of Smad3 with TGF-b type I receptor (TbRI) by blocking binding of Smad3 to SARA, suppressed subsequent phosphorylation of Smad3, reduced nuclear translocation of Smad2, Smad3, and Smad4, and downregulated the transcription of major fibrotic genes such as a-smooth muscle actin (a-SMA), collagen I, and fibronectin. Notably, intraperitoneal administration of GQ5 in rats immediately after unilateral ureteral obstruction (UUO) selectively inhibited Smad3 phosphorylation in UUO kidneys, suppressed renal expression of a-SMA, collagen I, and fibronectin, and resulted in impressive renal protection after obstructive injury. Late administration of GQ5 also effectively attenuated fibrotic lesions in obstructive nephropathy. In conclusion, our results suggest that GQ5 hinders renal fibrosis in rats by selective inhibition of TGF-b1-induced Smad3 phosphorylation.

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Section: Morphologic and Immunohistochemical Analysesmentioning

confidence: 99%

Retraction: GQ5 Hinders Renal Fibrosis in Obstructive Nephropathy by Selectively Inhibiting TGF-β–Induced Smad3 Phosphorylation

Nie

et al. 2015

Journal of the American Society of Nephrology

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“…In relaxin 2/2 mice, males developed worse age-dependent fibrosis than did female mice (49). An age-dependent development of fibrosis has also been noted in murine models of Hermansky-Pudlak disease (50). Finally, the infection of aged, but not young, mice with g-herpesvirus-68 results in the development of lung fibrosis, which is associated with epithelial cell endoplasmic reticulum stress and increased transforming growth factor-b (TGF-b) signaling in fibroblasts (51,52).…”

Section: Age-related Models Of Lung Fibrosismentioning

confidence: 77%

Animal Models of Fibrotic Lung Disease

Moore

Lawson

Oury

et al. 2013

Am J Respir Cell Mol Biol

350

308

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Interstitial lung fibrosis can develop as a consequence of occupational or medical exposure, as a result of genetic defects, and after trauma or acute lung injury leading to fibroproliferative acute respiratory distress syndrome, or it can develop in an idiopathic manner. The pathogenesis of each form of lung fibrosis remains poorly understood. They each result in a progressive loss of lung function with increasing dyspnea, and most forms ultimately result in mortality. To better understand the pathogenesis of lung fibrotic disorders, multiple animal models have been developed. This review summarizes the common and emerging models of lung fibrosis to highlight their usefulness in understanding the cell-cell and soluble mediator interactions that drive fibrotic responses. Recent advances have allowed for the development of models to study targeted injuries of Type II alveolar epithelial cells, fibroblastic autonomous effects, and targeted genetic defects. Repetitive dosing in some models has more closely mimicked the pathology of human fibrotic lung disease. We also have a much better understanding of the fact that the aged lung has increased susceptibility to fibrosis. Each of the models reviewed in this report offers a powerful tool for studying some aspect of fibrotic lung disease.Keywords: fibrosis; collagen; fibroblast; aging; cytokines Interstitial lung disease is often associated with the development of chronic fibrosis. These diseases are characterized clinically by progressive dyspnea, cough, restrictive physiology, and impaired gas exchange. Humans manifest many types of fibrotic lung disease (1). Among the diffuse parenchymal lung disorders (DPLDs) are diseases of known cause (e.g., drug-related, environmental exposures, or those associated with collagen vascular disease), the idiopathic interstitial pneumonias (IIPs), the granulomatous DPLDs (e.g., sarcoidosis), and rare noncategorized diseases, such as lymphangioleiomyomatosis. Idiopathic pulmonary fibrosis (IPF) is the most common disease within the category of IIPs, and is histopathologically identified as usual interstitial pneumonia (UIP). Additional diseases within the IIP category include desquamative interstitial pneumonia, respiratory bronchiolitis interstitial lung disease, acute interstitial pneumonia, cryptogenic organizing pneumonia, lymphocytic interstitial pneumonia, and nonspecific interstitial pneumonia (NSIP). IPF carries a poor prognosis, with a mean survival time of less than 5 years after diagnosis (2-5). Biopsies from a single patient can show heterogenous patterns consistent with both UIP and NSIP (4, 6, 7), suggesting that NSIP shares common pathogenic mechanisms with UIP.Diagnoses of patients with IPF who do not exhibit classic high-resolution computed tomography scan changes are confirmed by histopathologic evaluations of surgical lung biopsies, which demonstrate the pattern of UIP. Hallmark features of UIP include epithelial cell hyperplasia, basement membrane denudation, alveolar consolidation, and fibroblastic foci in a pa...

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“…Of note, lung fibrosis has only been observed in HPS-1, HPS-4 (4, 5), and HPS-2 (6) subtypes, which are associated with defects in the Biogenesis of Lysosome-Related Organelles Complex-3 or the Adaptor Protein-3 Complex. Interestingly, although HPS mono-mutant mice do not spontaneously develop lung fibrosis, HPS-1 and HPS-2 mice are highly susceptible to bleomycin-induced lung fibrosis (7), and mice with a combined HPS1 and HPS2 defect develop spontaneous pulmonary fibrosis (8,9).…”

Section: Hermansky-pudlak Syndrome Interstitial Pneumoniamentioning

confidence: 99%