RESUMEN
Fibrosis is a severe complication of chronic kidney disease (CKD). Progesterone, like other sex hormones, plays an important role in renal physiology, but its role in CKD is poorly understood. We investigated progesterone effect on renal fibrosis progression in the rat model of unilateral ureteral obstruction (UUO). Female rats were exposed to UUO, ovariectomy and progesterone administration after UUO with ovariectomy. Expression of key fibrosis markers, proinflammatory cytokines, levels of membrane-bound (PAQR5) and nuclear (PGR) progesterone receptors, and matrix metalloproteinase (MMP) activity were analyzed in the obstructed and intact rat kidney. In all groups exposed to UUO, decreased PAQR5 expression was observed in the obstructed kidney while in the contralateral kidney, it remained unaffected. We found increased mRNA levels for profibrotic COL1A1, FN1, MMP2, TIMP1, TIMP2, proinflammatory IL1α, IL1ß, and IL18, as well as elevated α-SMA and MMP9 proteins, collagen deposition, and MMP2 activity in all UUO kidneys. Progesterone had slight or no effect on the change in these markers. Thus, we demonstrate for the first time diminished sensitivity of the kidney to progesterone associated with renal fibrosis due to a severe decrease in PAQR5 expression that was accompanied by the lack of nephroprotection in a rat UUO model.
Asunto(s)
Receptores de Progesterona , Insuficiencia Renal Crónica , Obstrucción Ureteral , Animales , Femenino , Ratas , Fibrosis , Riñón/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Progesterona/farmacología , Insuficiencia Renal Crónica/complicaciones , Obstrucción Ureteral/complicaciones , Obstrucción Ureteral/tratamiento farmacológico , Obstrucción Ureteral/metabolismo , Receptores de Progesterona/metabolismoRESUMEN
The recent advances achieved in microscopy technology have led to a significant breakthrough in biological research. Super-resolution fluorescent microscopy now allows us to visualize subcellular structures down to the pin-pointing of the single molecules in them, while modern electron microscopy has opened new possibilities in the study of protein complexes in their native, intracellular environment at near-atomic resolution. Nonetheless, both fluorescent and electron microscopy have remained beset by their principal shortcomings: the reliance on labeling procedures and severe sample volume limitations, respectively. Soft X-ray microscopy is a candidate method that can compensate for the shortcomings of both technologies by making possible observation of the entirety of the cellular interior without chemical fixation and labeling with an isotropic resolution of 40-70 nm. This will thus bridge the resolution gap between light and electron microscopy (although this gap is being narrowed, it still exists) and resolve the issue of compatibility with the former, and possibly in the near future, the latter methods. This review aims to assess the current state of soft X-ray microscopy and its impact on our understanding of the subcellular organization. It also attempts to look into the future of X-ray microscopy, particularly as relates to its seamless integration into the cell biology toolkit.